research alcohol actions on brain, liver, pancreas, fetus, the The Director’s Column endocrine system and the immune system, has contributed Thanks for your gifts to our Center! to Crews’ insights. Alternatively, I suspect that he A. Leslie Morrow, Ph.D. assembled this diverse group of researchers to study alcohol Dean Ms. Carolyn S. Corn Mr. and Mrs. Ben Madore Associate Director, actions across so many systems of the body for the very ’’’ s C Ms. Harriet W. Crisp Bowles Center for (annual gifts oflub $5000 and above) Ms. Regina J. Mahon purpose of discovering how the complex systemic and Mr. and Mrs. Ray Damerell Alcohol Studies Dr. William Maixner molecular roles of alcohol go awry in the disease of Center Line James A. Bowles Mr. Lewis A. Dancy Mrs. Melissa M. Mann Bowles Center for Alcohol Studies alcoholism. Mr. John N. Howard, Jr. Mr. F. E. Danielus Mr. and Mrs. H. J. McCarthy School of Medicine, University of North Carolina at Chapel Hill Mr. and Mrs. Robert F. Schaecher Mr. Stephen M. Dean and Ms. Patricia L. Ms. Michelle McCarthy This integration of research across systems, organs, brain Ms. Ann Lewallen Spencer Amend Mr. and Mrs. Robert H. McConville, Jr. Dr. Fulton Crews’ brilliance can be attributed in part to regions, human development and the progression to Our mission is to conduct, coordinate, and promote basic and clinical research on the causes, prevention, and treatment of alcoholism and alcoholic disease. Tennessee Medical Foundation Ms. Elizabeth L. Deaver Mr. and Mrs. Loyce L. McCormick his understanding that human beings are not just a alcoholism is the hallmark of research in the Bowles Center Ms. Patricia Delaney Ms. Patricia E. McEvoy conglomerate of molecules and cells but complex organisms for Alcohol Studies. Dr. Fulton Crews has led this Center Volume 18, Number 1, March 2007 Mr. Charles H. Dodson Mr. Todd B. Melet with integrated organ, immune and endocrine systems. to promote such integration and has brought together a Chancel Mr. and Mrs. Leonard P. Duevel Mr. Afshin Meymandi Crews Lab Discovers Inflammatory Mechanisms Underlying (annual gifts lorof $2000 - $4999) Mr. and Mrs. David R. Eaton Alcohol effects on all these systems will ultimately impact team of researchers determined to find the causes and ’’’ s Club Mr. William L. Mitchell Mr. Samuel P. Echeveste Dr. Sheryl S. Moy many molecules and cells throughout the body. Hence, successful treatments for alcoholism in our lifetime. Alcohol-Induced Brain Damage Dr. Fulton T. Crews Ms. Sandy E. Englebert-Johnson Mr. Richard Munich systemic effects of alcohol on the entire body play a role in The Crews Lab is likely to find how preventing the Dr. A. Leslie Morrow and Dr. Michael C. Lish Mr. Steven Erickson Ms. Noreen Ordronneau the ultimate effects of alcohol on brain cells – including the proinflammatory effects of alcohol can prevent the Mr. and Mrs. J. Glenn Thurman “I don’t drink these days. I am allergic research technology have made it body against infections. Anti- Ms. Jewell Everhart Mr. and Mrs. Thomas M. Osler ability of alcohol to kill brain cells. Perhaps leading the development of alcoholism and promote recovery by First United Methodist Church Cary, NC, Inc to alcohol.....I break out in handcuffs.” possible to study biological correlates of inflammatory cytokines and growth Dr. and Mrs. David H. Overstreet Bowles Center for Alcohol Studies, where investigators preventing relapse. His lab has shown that heavy alcohol Bo Mr. and Mrs. Louis D. Fitzgerald Mrs. Sharon B. Owens -Robert Downey, Jr. alcoholism. Dr. Fulton Crews, alcohol factors also contribute to the diverse wles C use can kill brain cells, prevent neurogenesis and the (annual gifts oflub $1000 - $1999) Dr. Rebekah L. Fleming Mr. Lester E. Pace While Robert Downey, actions of this large family Ms. Claire L. Flowers Mr. Edward F. Paquette The Bowles Center for survival of new brain cells, and promote inflammation Jr.’s statement was made in of mediators. Dr. James C. Garbutt Mr. and Mrs. Hargrove Bowles III Dr. and Mrs. Peter H. Patterson Alcohol Studies across organ systems that persists in the brain. jest, it encapsulates an Crews’ interest in Mr. Kirk J. Bradley Ms. Arline P. Gertzoff Mr. Robert A. Pearce and Mrs. Margaret M. Inflammation may be the key to many diseases in many Tel. (919) 966-5678 earnest opinion often cytokines was sparked by his Mr. Nathaniel T. Harris Gifford Family Foundation Pearce organs, as well as the endocrine and immune systems, that Mr. and Mrs. Gary Giles Fax. (919) 966-5679 expressed by alcoholics: Bowles Center colleagues’ Mr. James Kerrigan Ms. Sylvia D. Perry disrupts normal function and leads to the demise of the Mr. Gary W. Gillis that alcohol provokes an research demonstrating that Mr. and Mrs. Dennis R. Schaecher Mr. and Mrs. M. Randolph Phillips organism – the human being. Thus, the importance of Ms. Karen W. Watkins Mr. and Mrs. Eugene W. Goodwillie, Jr. Plan On It, Inv. “allergic reaction” tumor necrosis factor-α To become involved in our mission, call Crews’ research extends far beyond the effects of alcohol Dr. and Mrs. Jack L. Wilhelm Mr. and Mrs. Phillip E. Grace Ms. Eleanor R. Pohl Elizabeth Thomas at (919) 966-4977 or email characterized by a unique (TNFα), a proinflam- Mr. and Mrs. H. S. Willson in honor of Ms. Shara S. Graham Ms. Gail M. Poitras [email protected]. on brain cells and molecules. physiological and matory cytokine released by Ms. Elizabeth C. Grant Ms. Jo Carole Willson, MS, LPC, LCAS Dr. Karen S. Popovich and Mr. Kenneth S. Latta The faculty of the Bowles Center for Alcoholism, along psychological sensitivity to specific liver cells, Ms. Betsy C. Wright Mr. Frances Hall Ms. Erin N. Potts with their advisors and consultants recognized the Mr. and Mrs. Richard P. Hall alcohol’s effects. The idea contributes to liver disease Mr. and Mrs. H. W. Potts For treatment information call UNC Health achievements and brilliance of Fulton Crews by awarding Mr. Richard N. Hanes Care’s Alcohol and Substance Abuse Program that an allergic reaction to in alcoholism. Chronic Dr. Liya Qin Crews Lab (Left to Right): Front Row: Jian Zou, PhD, Richard Hanes, Jun He, Dr. Joseph M. Harmon at (919) 966-6039 or (888) 457-7457. him the 2006 Bowles Lectureship Award. We are proud Friends of the Center Mr. Gary Ramer alcohol underlies PhD, Fulton Crews, PhD, Liya Qin, PhD, Tonya Hurst, Olivera Pluzarev, PhD. alcohol use causes a leaky gut, Harris Incorporated Ms. Susan Reaney of his leadership of our Center, and we are proud to work alcoholism was first with bacteria and ethanol Anonymous Dr. Jun He Mr. William F. Renn, Jr. with a great coach towards the championship in the introduced into the medical literature by researcher and Director of the University combining to stimulate the liver to make Anonymous Mr. and Mrs. Richard G. Hiskey Mr. and Mrs. Jon David Richmond tournament to reduce human suffering from alcoholism. the New York physician W. D. of North Carolina’s Skipper Bowles TNFα and other cytokines as part of an Anonymous Dr. and Dr. C. W. Hodge Mr. and Mrs. Mike Riley www.med.unc.edu/alcohol Anonymous Mr. John N. Howard Mr. Daniel Rosen and Ms. Claudia J. Niles Silkworth. In his pioneering 1937 paper, Center for Alcohol Studies, is at the inflammatory reaction. Present in excess, α Mr. and Mrs. Lawrence D. Adcock Mr. Stuart Howard Ms. Sarah Safrit Center Line, Vol. 18, No. 1 Published quarterly to bring readers a greater understanding of alcoholism research and the Center’s mission. “Alcoholism as a Manifestation of forefront of efforts to elucidate the TNF and other cytokines cause cellular Mr. and Mrs. William R. Allen III Ms. Marilyn L. Huff Mr. and Mrs. George L. Schueppert A. Leslie Morrow, Ph.D., Editor-in-Chief; Elizabeth Thomas, Managing Editor; Jane Saiers, Ph.D., Science Writer Allergy,” Silkworth argued that neurobiology of alcoholism. Crews says toxicity and over time contribute to Mr. and Mrs. Michael R. Amend Ms. Beth Ann Huskamp Ms. Angela Sercer alcoholism is a physical malady with a that, while Silkworth’s concept of alcoholic liver disease. Crews, whose Mr. and Mrs. G. E. Barnes Mr. and Mrs. Doug Hutchins Mr. J. Lansing Smith UNC Bowles Center for Alcohol Studies Non-Profit Organization development and course analogous in alcoholism as a classical allergic reaction primary research focus is alcohol- Ms. Helen J. Benson Mr. and Mrs. William M. Iacuessa Mr. and Mrs. Ralph N. Smith CB# 7178, Thurston-Bowles Building US Postage many respects to allergies such as hay has not been fully supported, remarkable induced brain degeneration, speculated Dr. Wilbert W. Blackman Mr. Jon Irish and Mrs. Janet Head Ms. Rhonda Steele 5 PAID Mr. and Mrs. William M. Borndahl Mr. Thomas H. Jewett Mr. and Mrs. Jack M. Streb University of North Carolina at Chapel Hill Permit No. 177 fever. His conceptualization of parallels between allergic responses and that cytokines might also contribute to Mr. and Mrs. Erskine B. Bowles Mr. and Mrs. Roger L. Johnson Ms. Rory M. Taylor Chapel Hill, North Carolina 27599-7178 Chapel Hill, NC 27599-1800 alcoholism as an allergic state ran the body’s response to alcohol have been neurodegeneration in alcoholism. Ms. Roxanne J. Boyd Mr. Daniel H. Kim Mrs. Alice W. Thomason counter to the prevailing view of revealed. In short, both allergic Cytokines are produced in the brain by Mr. and Mrs. Richard H. Bradford Dr. Darin J. Knapp and Dr. Jane Saiers Mr. and Mrs. C. Duke Thompson alcoholism as a moral failing and responses and the body’s response to microglia, which are the brain’s immune Mr. and Mrs. Gerald L. Brown Mr. Mong Kong Ms. Sarah K. Tiller continues to resonate among today’s alcohol involve inflammatory processes cells. In a study in rats, Crews and his Mr. and Mrs. David W. Buck Dr. Marcia A. Koomen Mr. and Mrs. Stephen G. Toigo alcoholics and recovering alcoholics, who in which cytokines play key roles. colleagues discovered that a binge Ms. Jacquelyn G. Burgess Dr. Sandeep Kumar and Dr. Himi Saxena Mr. and Mrs. Lane VanderHoek Ms. Erin Burk-Tappy Ms. Mary A. Lambert Mr. Frans L. Victorson still widely cite and discuss Silkworth’s Cytokines constitute a diverse group of alcohol treatment regimen modeling the Mr. and Mrs. J. Brian Butler Mr. Benajmin M. Lancaster, Jr Mrs. Maureen Vollmer work. proteins that regulate immune drinking pattern of human alcoholics in Ms. Kimberley J. Campbell Ms. Edmonia L. Lang Ms. Walker G. Weigel In the 1930s, before the advent of responses, inflammation, hormones, fact caused microglial activation Ms. Michelle Carter Mr. Brian Lapham and Dr. Donita Robinson Mr. and Mrs. Thomas W. Whisnant neurobiological research on alcohol wound healing, and communication accompanied by persistent increases in Mr. Michael L. Case Ms. Doris L. Lee Mr. and Mrs. Paul S. Wilcox effects, Silkworth had no means of among cells throughout the body. Only the proinflammatory cytokines TNFα, Mr. and Mrs. Taylor M. Chambers Mr. Bernard Leewood Ms. M. E. Wilkie garnering biological support for his recently have they been studied in the interleukin-1 beta (IL-1β), and Mr. and Mrs. Elliot Chase Dr. Joan Lenowitz Mr. and Mrs. David C. Wright Ms. Marie W. B. Cherry Ms. Vicky Lepoutre Mr. and Mrs. Norman A. Wulf hypothesis of alcoholism as an allergic brain. The action of pro-inflammatory monocyte chemotactic protein-1 Mr. and Mrs. H. J. Cobb Mr. Johnathan Lorencz Dr. Jian Y. Zou reaction. Subsequent advances in cytokines is crucial for defending the (MCP-1). These cytokine changes were Ms. Meghan W. Cody This document is supported by subscriptions and donations to the Bowles Center for Alcohol Studies; All research partially funded by NIAAA. Ms. Shirlyn R. MacPherson Continued on next page Crews Lab Continued ASAP story continued Continued from previous page One of the myriad pro-inflammatory α α accompanied by binge-induced brain actions of TNF is activation of nuclear further increases in NF- in brain TNF . Although “We already have a night group in place but have growing ASAP also works very closely with the UNC Department κ κ κ damage. These findings are consistent with factor B (NF- B), a transcription factor B DNA-binding more research needs to be numbers of patients who are unable to join us in the of Psychiatry’s Substance Abuse Clinic, headed by J.C. Crews’ hypothesis that uncontrolled that regulates genes’ production of proteins activity and trigger done, it is possible that evening.” said Renn. “We wanted to offer an alternative Garbutt, M.D. Garbutt, also the medical director for ASAP, activation of microglia directly releases by binding to particular sites on DNA. NF- various inflammatory increased anti-inflammatory for those patients.” is an expert in the pharmacological treatment of alcohol κ cytokines that are toxic to neurons. B is a pro-inflammatory transcription cascades. Alcohol cytokines could contribute to In addition to the day and evening groups, a walk-in clinic dependence, as well as a faculty member of the Bowles Center Knowing that liver cells, like the brain’s factor that causes genes to produce perpetuates inflammation the health benefits is in the planning stages. Renn expects that the new walk- for Alcohol Studies. microglia, overproduce cytokines when potentially cell-damaging oxidative between organs as when associated with low levels of in clinic will begin in early April. A Brief Intervention While ASAP does not offer free services, every effort is α exposed to alcohol, Crews hypothesized enzymes such as nicotinamide adenine TNF produced in the drinking. Model, along with a clinical interview, will be made available made to treat those who seek help. UNC Health Care accepts that the brain might be also exposed to dinucleotide phosphate-oxidase and liver affects inflammatory “Many physiological and to walk-ins on Fridays from 10 a.m. until 2 p.m. This new most forms of insurance, Medicare and Medicaid, and financial cyclooxygenase-2 (COX2), as well as more responses in the brain psychological aspects of walk-in format will operate on a first come, first served counselors will work individually with each patient to develop Fulton T. Crews, Ph.D. cytokines originating from the liver in α schedule and will allow ASAP staff to meet and evaluate ------individuals who consume excessive alcohol. TNF and other proinflammatory (Figure). Crews found alcoholism could be a manageable payment plan. “This is not a crisis service,” Liver-originating cytokines such as TNFα cytokines. Crews showed that alcohol that the liver makes anti- secondary to the cytokine even more patients who seek treatment for addiction. “I Renn stressed. “Those individuals who are in medical or κ are released into the bloodstream to cause increased NF- B DNA-binding activity in inflammatory cytokines changes we have encourage everyone who is thinking about treatment to psychiatric crisis should go directly to UNC Hospital.” Affiliations inflammation throughout the body. To brain. Alcohol, proinflammatory cytokines, in response to alcohol discovered,” notes Crews. come in. Let’s start the conversation,” Renn said. “We really work together attempting to treat, prevent and Director, Bowles Center for Alcohol κ that in time suppress Figure: Ethanol increases systemic and brain cytokines. Alcohol “Understanding cytokines Renn and his staff, which consists of four masters-level Studies; Professor, Departments of explore the hypothesis that peripheral NF- B DNA-binding, and oxidative stress cure alcoholism and drug addiction. We would like treatment (ethanol-ETOH) is consumed orally, enters the gut and makes the gut addiction therapists, work incredibly well as a team and have Pharmacology and Psychiatry. TNFα affects inflammation in brain, Crews were found to interact to promote proinflammatory responses, leaky allowing endotoxin (lipopolysaccharide-LPS) to enter the could provide new diagnostic to be available for everyone who needs it,” said Renn. “Our and his collaborators used the bacterial neurodegeneration contributing to alcohol- whereas ethanol suppresses circulation. LPS and ethanol activate the liver to produce cytokines and therapeutic approaches to treated hundreds of patients since ASAP began in 1998. door is open, and we’re not going to turn anyone away.” α α Education and Training endotoxin lipopolysaccharide (LPS) to associated brain damage as well as other proinflammatory cytokines in such as TNF . Ethanol and TNF enter the brain and increase brain many chronic diseases, Treatment lasts anywhere from three months up to a year For more information or to make an appointment with ASAP, cytokine synthesis. Within brain, microglia, astrocytes and neurons Post-doctoral training in pharmacol- stimulate TNFα production in mice. They neurodegenerative conditions including brain, an effect that might particularly those known to be and ranges from intensive outpatient to more traditional call (919) 966-6039/ (888) 457-7457, or visit ogy, National Institutes of Health, respond by altering gene expression that contributes to alcoholic found that elevations in TNFα levels in the Alzheimer’s disease and Parkinson’s disease. contribute to the previously neurodegeneration. influenced by alcohol.” outpatient clinic visits for both substance abuse and mental http://www.med.unc.edu/alcohol/asap. Bethesda, MD, 1980; health. Ph.D., Pharmacology, University of liver, serum, and brain coincided shortly An antioxidant (butylated hydroxytoluene) observed pro-longed increases κ Michigan, Ann Arbor, 1978; after LPS administration. However, reduced NF- B DNA-binding activity and B.S., Physiology, Syracuse University, whereas TNFα levels declined to normal in alcohol-induced neurotoxicity both in vitro THANKS TO ALL OF OUR FRIENDS! NY, 1971. liver and in serum within a short period of and in vivo using the binge model of alcohol ASAP Clinic- A National Model for Alcohol and Substance Abuse Treatment time, TNFα levels remained elevated in the neurodegeneration. Binge alcohol Your willingness to share your resources has assisted us in many ways over the years. treatment was associated with microglial Recent Publications brain for up to 10 months. In another The Alcohol and Substance Over the past several years, ASAP activation, increased NF-κB DNA-binding experiment, Crews and his colleagues Abuse Program (ASAP) at has been involved in a number of SUPPORTING fellows in the research labs investigating the mechanisms of alcoholic pathology in α activity, and brain damage. The brain Qin, L, Wu, X, Block, ML, Liu, Y, Breese, systemically administered LPS or TNF to UNC uses cutting-edge clinical trails. Its current research the brain, fetus and liver. damage was reversed by antioxidant GR, Hong, JS, Knapp, DJ, Crews, FT. normal mice and to a group of mice bred to approaches based on the most studies focus on the use of Systemic LPS causes chronic α treatment. The results suggest a crucial role genetically lack the TNF receptor, a current and relevant research pharmacotherapy to treat alcohol EXPANDING our Intensive Outpatient Alcohol and Substance Abuse Treatment Program. neuroinflammation and progressive of NF-κB in neurotoxicity caused by receptor previously shown to transport on alcoholism and substance and drug dependence. One study neurodegeneration. Glia, 55(5): 453- α oxidative stress, including that associated 62 (2007). TNF from serum to brain. In the normal abuse. ASAP utilizes measures the efficacy of the drug α with alcohol, and support the hypothesis RECRUITING the top research faculty from around the world to carry out our mission to make mice, but not in mice lacking the TNF research-based protocols, and Aripiprazole in conjunction with that neuroinflammation contributes to discoveries on the causes, prevention and treatment of alcoholism and alcoholic disease. Crews, FT, Nixon, K, Kim, D, Joseph, receptor, systemic administration of LPS or each addiction therapist on the use of weekly, psychosocial J, Shukitt-Hale, B, Qin, L, Zou, J. BHT α alcohol-induced brain damage. TNF was associated with activation of staff is trained in motivational treatment sessions. The other study blocks NF-kappaB activation and Crews and his colleagues have recently microglia; increased levels of pro- interviewing, cognitive- compares those with alcohol REACHING thousands of students and adults across North Carolina and the world through our ethanol-induced brain damage. Al- α extended their work to humans. In a study cohol Clin Exp Res, 30(11): 1938-49 inflammatory cytokines, specifically TNF , behavioral therapies and dependence who prefer sweets to education and prevention programs. β with human postmortem brains supplied by (2006). MCP-1, and IL-1 , in the brain; and loss psychosocial strategies to those who do not and their response the Australia Brain Donor Program, they Yes, I would like to join the effort to cure alcoholism in our lifetime. of neurons in the substantia nigra, a brain ensure medication compliance. to Naltrexone. Zou, J, Crews, FT. CREB and NF- observed neuroinflammation and increased region known to have lots of microglia. The program, part of UNC “These research efforts have been ___$50 ___$150 ___$250 ___$500 other _____ kappaB transcription factors regulate morphological signs of microglial activation. ASAP Staff (Left to Right): Ben Lancaster, LPC, Bill Renn, LCSW, sensitivity to excitotoxic and oxidative These experiments illustrate how Healthcare, the Bowles Center rewarding to the staff and have been ___$1000 Bowles Club ___$2000 Chancellor’s Club ___$5000 Dean’s Club Furthermore, they found that levels of the LCAS, Tom Watkins, LCAS, Arleta Brooks, CNA, Kathy Grace, LPC, stress induced neuronal cell death. inflammation originating outside the brain for Alcohol Studies and the J.C. Garbutt, MD. published in two major journals. Please return to: proinflammatory cytokine MCP-1 were __ Check enclosed, payable to the Bowles Center for Alcohol Studies Cell Mol Neurobiol, 26(4-6): 383-403 can trigger persistent brain inflammation Department of Psychiatry, specializes in individualized Although there are no medications dispensed or available at Bowles CAS significantly higher in the brains of __ My company matches gifts. The form is attached. (2006). that is associated with brain damage. treatment based on the unique needs, motivation and personal this clinic, our efforts led to the FDA approval of long-acting c/o Elizabeth Thomas α alcoholics than the brains of control, Elevated TNF in the periphery induced goals of each patient. injectable naltrexone for the treatment of alcohol dependence,” __ I would prefer to remain anonymous. Crews, FT, Bechara, R, Brown, LA, α moderate-drinking individuals. CB#7178, UNC-CH brain TNF , activated microglia, and “ASAP has the ability to treat individuals who need to said Renn. Guidot, DM, Mandrekar, P, Oak, S, Considered in aggregate, Crews’ findings Chapel Hill, NC 27599 Donations can also be made online through the Medical Foundation of NC at caused delayed neurodegeneration. “These commit to lifelong abstinence, as well as those patients who The Program is also heralding new initiatives that will make Qin, L, Szabo, G, Wheeler, M, Zou, J. α suggest that excessive alcohol consumption http://medicalfoundationofnc.org/donate.shtml Cytokines and alcohol. Alcohol Clin results suggest that when TNF is elevated are much more ambivalent about the damage that their alcohol treatment for patients even more convenient and accessible. sets off a spreading cytokine process Exp Res, 30(4): 720-30 (2006). in serum, the brain is also in trouble,” says or drug addiction is causing them,” said Bill Renn, ASAP In February, ASAP added a Day Treatment Group that meets (Figure). Alcohol disrupts cytokines both Crews. “One fascinating aspect of this Director and Associate Professor of Psychiatry at UNC. “Our four days a week, Monday through Thursday, from 1:30-3 within organs and between organs. For discovery is that serum cytokine levels models of care and our approaches are based on the latest p.m. The treatment sessions focus on a curriculum that Website example, alcohol perpetuates inflammation NAME E-MAIL ADDRESS return to normal, whereas the brain, once research and literature in the field, and I consider this to be a includes gaining and maintaining abstinence, relapse http://www.med.unc.edu/alcohol/ α within the brain when it induces NF-κB primed by serum TNF , has elevated national model for care based on the experience and expertise prevention, key coping and refusal skills, spirituality, ADDRESS CITY faculty/CrewsFT/Crews.htm DNA-binding activity, which activates proinflammatory cytokine levels for long of the staff.” meditation, and other science-based interventions. periods, perhaps forever.” inflammatory mediators that stimulate STATE AND COUNTRY ZIP/POSTAL CODE Crews Lab Continued ASAP story continued Continued from previous page One of the myriad pro-inflammatory α α accompanied by binge-induced brain actions of TNF is activation of nuclear further increases in NF- in brain TNF . Although “We already have a night group in place but have growing ASAP also works very closely with the UNC Department κ κ κ damage. These findings are consistent with factor B (NF- B), a transcription factor B DNA-binding more research needs to be numbers of patients who are unable to join us in the of Psychiatry’s Substance Abuse Clinic, headed by J.C. Crews’ hypothesis that uncontrolled that regulates genes’ production of proteins activity and trigger done, it is possible that evening.” said Renn. “We wanted to offer an alternative Garbutt, M.D. Garbutt, also the medical director for ASAP, activation of microglia directly releases by binding to particular sites on DNA. NF- various inflammatory increased anti-inflammatory for those patients.” is an expert in the pharmacological treatment of alcohol κ cytokines that are toxic to neurons. B is a pro-inflammatory transcription cascades. Alcohol cytokines could contribute to In addition to the day and evening groups, a walk-in clinic dependence, as well as a faculty member of the Bowles Center Knowing that liver cells, like the brain’s factor that causes genes to produce perpetuates inflammation the health benefits is in the planning stages. Renn expects that the new walk- for Alcohol Studies. microglia, overproduce cytokines when potentially cell-damaging oxidative between organs as when associated with low levels of in clinic will begin in early April. A Brief Intervention While ASAP does not offer free services, every effort is α exposed to alcohol, Crews hypothesized enzymes such as nicotinamide adenine TNF produced in the drinking. Model, along with a clinical interview, will be made available made to treat those who seek help. UNC Health Care accepts that the brain might be also exposed to dinucleotide phosphate-oxidase and liver affects inflammatory “Many physiological and to walk-ins on Fridays from 10 a.m. until 2 p.m. This new most forms of insurance, Medicare and Medicaid, and financial cyclooxygenase-2 (COX2), as well as more responses in the brain psychological aspects of walk-in format will operate on a first come, first served counselors will work individually with each patient to develop Fulton T. Crews, Ph.D. cytokines originating from the liver in α schedule and will allow ASAP staff to meet and evaluate ------individuals who consume excessive alcohol. TNF and other proinflammatory (Figure). Crews found alcoholism could be a manageable payment plan. “This is not a crisis service,” Liver-originating cytokines such as TNFα cytokines. Crews showed that alcohol that the liver makes anti- secondary to the cytokine even more patients who seek treatment for addiction. “I Renn stressed. “Those individuals who are in medical or κ are released into the bloodstream to cause increased NF- B DNA-binding activity in inflammatory cytokines changes we have encourage everyone who is thinking about treatment to psychiatric crisis should go directly to UNC Hospital.” Affiliations inflammation throughout the body. To brain. Alcohol, proinflammatory cytokines, in response to alcohol discovered,” notes Crews. come in. Let’s start the conversation,” Renn said. “We really work together attempting to treat, prevent and Director, Bowles Center for Alcohol κ that in time suppress Figure: Ethanol increases systemic and brain cytokines. Alcohol “Understanding cytokines Renn and his staff, which consists of four masters-level Studies; Professor, Departments of explore the hypothesis that peripheral NF- B DNA-binding, and oxidative stress cure alcoholism and drug addiction. We would like treatment (ethanol-ETOH) is consumed orally, enters the gut and makes the gut addiction therapists, work incredibly well as a team and have Pharmacology and Psychiatry. TNFα affects inflammation in brain, Crews were found to interact to promote proinflammatory responses, leaky allowing endotoxin (lipopolysaccharide-LPS) to enter the could provide new diagnostic to be available for everyone who needs it,” said Renn. “Our and his collaborators used the bacterial neurodegeneration contributing to alcohol- whereas ethanol suppresses circulation. LPS and ethanol activate the liver to produce cytokines and therapeutic approaches to treated hundreds of patients since ASAP began in 1998. door is open, and we’re not going to turn anyone away.” α α Education and Training endotoxin lipopolysaccharide (LPS) to associated brain damage as well as other proinflammatory cytokines in such as TNF . Ethanol and TNF enter the brain and increase brain many chronic diseases, Treatment lasts anywhere from three months up to a year For more information or to make an appointment with ASAP, cytokine synthesis. Within brain, microglia, astrocytes and neurons Post-doctoral training in pharmacol- stimulate TNFα production in mice. They neurodegenerative conditions including brain, an effect that might particularly those known to be and ranges from intensive outpatient to more traditional call (919) 966-6039/ (888) 457-7457, or visit ogy, National Institutes of Health, respond by altering gene expression that contributes to alcoholic found that elevations in TNFα levels in the Alzheimer’s disease and Parkinson’s disease. contribute to the previously neurodegeneration. influenced by alcohol.” outpatient clinic visits for both substance abuse and mental http://www.med.unc.edu/alcohol/asap. Bethesda, MD, 1980; health. Ph.D., Pharmacology, University of liver, serum, and brain coincided shortly An antioxidant (butylated hydroxytoluene) observed pro-longed increases κ Michigan, Ann Arbor, 1978; after LPS administration. However, reduced NF- B DNA-binding activity and B.S., Physiology, Syracuse University, whereas TNFα levels declined to normal in alcohol-induced neurotoxicity both in vitro THANKS TO ALL OF OUR FRIENDS! NY, 1971. liver and in serum within a short period of and in vivo using the binge model of alcohol ASAP Clinic- A National Model for Alcohol and Substance Abuse Treatment time, TNFα levels remained elevated in the neurodegeneration. Binge alcohol Your willingness to share your resources has assisted us in many ways over the years. treatment was associated with microglial Recent Publications brain for up to 10 months. In another The Alcohol and Substance Over the past several years, ASAP activation, increased NF-κB DNA-binding experiment, Crews and his colleagues Abuse Program (ASAP) at has been involved in a number of SUPPORTING fellows in the research labs investigating the mechanisms of alcoholic pathology in α activity, and brain damage. The brain Qin, L, Wu, X, Block, ML, Liu, Y, Breese, systemically administered LPS or TNF to UNC uses cutting-edge clinical trails. Its current research the brain, fetus and liver. damage was reversed by antioxidant GR, Hong, JS, Knapp, DJ, Crews, FT. normal mice and to a group of mice bred to approaches based on the most studies focus on the use of Systemic LPS causes chronic α treatment. The results suggest a crucial role genetically lack the TNF receptor, a current and relevant research pharmacotherapy to treat alcohol EXPANDING our Intensive Outpatient Alcohol and Substance Abuse Treatment Program. neuroinflammation and progressive of NF-κB in neurotoxicity caused by receptor previously shown to transport on alcoholism and substance and drug dependence. One study neurodegeneration. Glia, 55(5): 453- α oxidative stress, including that associated 62 (2007). TNF from serum to brain. In the normal abuse. ASAP utilizes measures the efficacy of the drug α with alcohol, and support the hypothesis RECRUITING the top research faculty from around the world to carry out our mission to make mice, but not in mice lacking the TNF research-based protocols, and Aripiprazole in conjunction with that neuroinflammation contributes to discoveries on the causes, prevention and treatment of alcoholism and alcoholic disease. Crews, FT, Nixon, K, Kim, D, Joseph, receptor, systemic administration of LPS or each addiction therapist on the use of weekly, psychosocial J, Shukitt-Hale, B, Qin, L, Zou, J. BHT α alcohol-induced brain damage. TNF was associated with activation of staff is trained in motivational treatment sessions. The other study blocks NF-kappaB activation and Crews and his colleagues have recently microglia; increased levels of pro- interviewing, cognitive- compares those with alcohol REACHING thousands of students and adults across North Carolina and the world through our ethanol-induced brain damage. Al- α extended their work to humans. In a study cohol Clin Exp Res, 30(11): 1938-49 inflammatory cytokines, specifically TNF , behavioral therapies and dependence who prefer sweets to education and prevention programs. β with human postmortem brains supplied by (2006). MCP-1, and IL-1 , in the brain; and loss psychosocial strategies to those who do not and their response the Australia Brain Donor Program, they Yes, I would like to join the effort to cure alcoholism in our lifetime. of neurons in the substantia nigra, a brain ensure medication compliance. to Naltrexone. Zou, J, Crews, FT. CREB and NF- observed neuroinflammation and increased region known to have lots of microglia. The program, part of UNC “These research efforts have been ___$50 ___$150 ___$250 ___$500 other _____ kappaB transcription factors regulate morphological signs of microglial activation. ASAP Staff (Left to Right): Ben Lancaster, LPC, Bill Renn, LCSW, sensitivity to excitotoxic and oxidative These experiments illustrate how Healthcare, the Bowles Center rewarding to the staff and have been ___$1000 Bowles Club ___$2000 Chancellor’s Club ___$5000 Dean’s Club Furthermore, they found that levels of the LCAS, Tom Watkins, LCAS, Arleta Brooks, CNA, Kathy Grace, LPC, stress induced neuronal cell death. inflammation originating outside the brain for Alcohol Studies and the J.C. Garbutt, MD. published in two major journals. Please return to: proinflammatory cytokine MCP-1 were __ Check enclosed, payable to the Bowles Center for Alcohol Studies Cell Mol Neurobiol, 26(4-6): 383-403 can trigger persistent brain inflammation Department of Psychiatry, specializes in individualized Although there are no medications dispensed or available at Bowles CAS significantly higher in the brains of __ My company matches gifts. The form is attached. (2006). that is associated with brain damage. treatment based on the unique needs, motivation and personal this clinic, our efforts led to the FDA approval of long-acting c/o Elizabeth Thomas α alcoholics than the brains of control, Elevated TNF in the periphery induced goals of each patient. injectable naltrexone for the treatment of alcohol dependence,” __ I would prefer to remain anonymous. Crews, FT, Bechara, R, Brown, LA, α moderate-drinking individuals. CB#7178, UNC-CH brain TNF , activated microglia, and “ASAP has the ability to treat individuals who need to said Renn. Guidot, DM, Mandrekar, P, Oak, S, Considered in aggregate, Crews’ findings Chapel Hill, NC 27599 Donations can also be made online through the Medical Foundation of NC at caused delayed neurodegeneration. “These commit to lifelong abstinence, as well as those patients who The Program is also heralding new initiatives that will make Qin, L, Szabo, G, Wheeler, M, Zou, J. α suggest that excessive alcohol consumption http://medicalfoundationofnc.org/donate.shtml Cytokines and alcohol. Alcohol Clin results suggest that when TNF is elevated are much more ambivalent about the damage that their alcohol treatment for patients even more convenient and accessible. sets off a spreading cytokine process Exp Res, 30(4): 720-30 (2006). in serum, the brain is also in trouble,” says or drug addiction is causing them,” said Bill Renn, ASAP In February, ASAP added a Day Treatment Group that meets (Figure). Alcohol disrupts cytokines both Crews. “One fascinating aspect of this Director and Associate Professor of Psychiatry at UNC. “Our four days a week, Monday through Thursday, from 1:30-3 within organs and between organs. For discovery is that serum cytokine levels models of care and our approaches are based on the latest p.m. The treatment sessions focus on a curriculum that Website example, alcohol perpetuates inflammation NAME E-MAIL ADDRESS return to normal, whereas the brain, once research and literature in the field, and I consider this to be a includes gaining and maintaining abstinence, relapse http://www.med.unc.edu/alcohol/ α within the brain when it induces NF-κB primed by serum TNF , has elevated national model for care based on the experience and expertise prevention, key coping and refusal skills, spirituality, ADDRESS CITY faculty/CrewsFT/Crews.htm DNA-binding activity, which activates proinflammatory cytokine levels for long of the staff.” meditation, and other science-based interventions. periods, perhaps forever.” inflammatory mediators that stimulate STATE AND COUNTRY ZIP/POSTAL CODE Crews Lab Continued ASAP story continued Continued from previous page One of the myriad pro-inflammatory α α accompanied by binge-induced brain actions of TNF is activation of nuclear further increases in NF- in brain TNF . Although “We already have a night group in place but have growing ASAP also works very closely with the UNC Department κ κ κ damage. These findings are consistent with factor B (NF- B), a transcription factor B DNA-binding more research needs to be numbers of patients who are unable to join us in the of Psychiatry’s Substance Abuse Clinic, headed by J.C. Crews’ hypothesis that uncontrolled that regulates genes’ production of proteins activity and trigger done, it is possible that evening.” said Renn. “We wanted to offer an alternative Garbutt, M.D. Garbutt, also the medical director for ASAP, activation of microglia directly releases by binding to particular sites on DNA. NF- various inflammatory increased anti-inflammatory for those patients.” is an expert in the pharmacological treatment of alcohol κ cytokines that are toxic to neurons. B is a pro-inflammatory transcription cascades. Alcohol cytokines could contribute to In addition to the day and evening groups, a walk-in clinic dependence, as well as a faculty member of the Bowles Center Knowing that liver cells, like the brain’s factor that causes genes to produce perpetuates inflammation the health benefits is in the planning stages. Renn expects that the new walk- for Alcohol Studies. microglia, overproduce cytokines when potentially cell-damaging oxidative between organs as when associated with low levels of in clinic will begin in early April. A Brief Intervention While ASAP does not offer free services, every effort is α exposed to alcohol, Crews hypothesized enzymes such as nicotinamide adenine TNF produced in the drinking. Model, along with a clinical interview, will be made available made to treat those who seek help. UNC Health Care accepts that the brain might be also exposed to dinucleotide phosphate-oxidase and liver affects inflammatory “Many physiological and to walk-ins on Fridays from 10 a.m. until 2 p.m. This new most forms of insurance, Medicare and Medicaid, and financial cyclooxygenase-2 (COX2), as well as more responses in the brain psychological aspects of walk-in format will operate on a first come, first served counselors will work individually with each patient to develop Fulton T. Crews, Ph.D. cytokines originating from the liver in α schedule and will allow ASAP staff to meet and evaluate ------individuals who consume excessive alcohol. TNF and other proinflammatory (Figure). Crews found alcoholism could be a manageable payment plan. “This is not a crisis service,” Liver-originating cytokines such as TNFα cytokines. Crews showed that alcohol that the liver makes anti- secondary to the cytokine even more patients who seek treatment for addiction. “I Renn stressed. “Those individuals who are in medical or κ are released into the bloodstream to cause increased NF- B DNA-binding activity in inflammatory cytokines changes we have encourage everyone who is thinking about treatment to psychiatric crisis should go directly to UNC Hospital.” Affiliations inflammation throughout the body. To brain. Alcohol, proinflammatory cytokines, in response to alcohol discovered,” notes Crews. come in. Let’s start the conversation,” Renn said. “We really work together attempting to treat, prevent and Director, Bowles Center for Alcohol κ that in time suppress Figure: Ethanol increases systemic and brain cytokines. Alcohol “Understanding cytokines Renn and his staff, which consists of four masters-level Studies; Professor, Departments of explore the hypothesis that peripheral NF- B DNA-binding, and oxidative stress cure alcoholism and drug addiction. We would like treatment (ethanol-ETOH) is consumed orally, enters the gut and makes the gut addiction therapists, work incredibly well as a team and have Pharmacology and Psychiatry. TNFα affects inflammation in brain, Crews were found to interact to promote proinflammatory responses, leaky allowing endotoxin (lipopolysaccharide-LPS) to enter the could provide new diagnostic to be available for everyone who needs it,” said Renn. “Our and his collaborators used the bacterial neurodegeneration contributing to alcohol- whereas ethanol suppresses circulation. LPS and ethanol activate the liver to produce cytokines and therapeutic approaches to treated hundreds of patients since ASAP began in 1998. door is open, and we’re not going to turn anyone away.” α α Education and Training endotoxin lipopolysaccharide (LPS) to associated brain damage as well as other proinflammatory cytokines in such as TNF . Ethanol and TNF enter the brain and increase brain many chronic diseases, Treatment lasts anywhere from three months up to a year For more information or to make an appointment with ASAP, cytokine synthesis. Within brain, microglia, astrocytes and neurons Post-doctoral training in pharmacol- stimulate TNFα production in mice. They neurodegenerative conditions including brain, an effect that might particularly those known to be and ranges from intensive outpatient to more traditional call (919) 966-6039/ (888) 457-7457, or visit ogy, National Institutes of Health, respond by altering gene expression that contributes to alcoholic found that elevations in TNFα levels in the Alzheimer’s disease and Parkinson’s disease. contribute to the previously neurodegeneration. influenced by alcohol.” outpatient clinic visits for both substance abuse and mental http://www.med.unc.edu/alcohol/asap. Bethesda, MD, 1980; health. Ph.D., Pharmacology, University of liver, serum, and brain coincided shortly An antioxidant (butylated hydroxytoluene) observed pro-longed increases κ Michigan, Ann Arbor, 1978; after LPS administration. However, reduced NF- B DNA-binding activity and B.S., Physiology, Syracuse University, whereas TNFα levels declined to normal in alcohol-induced neurotoxicity both in vitro THANKS TO ALL OF OUR FRIENDS! NY, 1971. liver and in serum within a short period of and in vivo using the binge model of alcohol ASAP Clinic- A National Model for Alcohol and Substance Abuse Treatment time, TNFα levels remained elevated in the neurodegeneration. Binge alcohol Your willingness to share your resources has assisted us in many ways over the years. treatment was associated with microglial Recent Publications brain for up to 10 months. In another The Alcohol and Substance Over the past several years, ASAP activation, increased NF-κB DNA-binding experiment, Crews and his colleagues Abuse Program (ASAP) at has been involved in a number of SUPPORTING fellows in the research labs investigating the mechanisms of alcoholic pathology in α activity, and brain damage. The brain Qin, L, Wu, X, Block, ML, Liu, Y, Breese, systemically administered LPS or TNF to UNC uses cutting-edge clinical trails. Its current research the brain, fetus and liver. damage was reversed by antioxidant GR, Hong, JS, Knapp, DJ, Crews, FT. normal mice and to a group of mice bred to approaches based on the most studies focus on the use of Systemic LPS causes chronic α treatment. The results suggest a crucial role genetically lack the TNF receptor, a current and relevant research pharmacotherapy to treat alcohol EXPANDING our Intensive Outpatient Alcohol and Substance Abuse Treatment Program. neuroinflammation and progressive of NF-κB in neurotoxicity caused by receptor previously shown to transport on alcoholism and substance and drug dependence. One study neurodegeneration. Glia, 55(5): 453- α oxidative stress, including that associated 62 (2007). TNF from serum to brain. In the normal abuse. ASAP utilizes measures the efficacy of the drug α with alcohol, and support the hypothesis RECRUITING the top research faculty from around the world to carry out our mission to make mice, but not in mice lacking the TNF research-based protocols, and Aripiprazole in conjunction with that neuroinflammation contributes to discoveries on the causes, prevention and treatment of alcoholism and alcoholic disease. Crews, FT, Nixon, K, Kim, D, Joseph, receptor, systemic administration of LPS or each addiction therapist on the use of weekly, psychosocial J, Shukitt-Hale, B, Qin, L, Zou, J. BHT α alcohol-induced brain damage. TNF was associated with activation of staff is trained in motivational treatment sessions. The other study blocks NF-kappaB activation and Crews and his colleagues have recently microglia; increased levels of pro- interviewing, cognitive- compares those with alcohol REACHING thousands of students and adults across North Carolina and the world through our ethanol-induced brain damage. Al- α extended their work to humans. In a study cohol Clin Exp Res, 30(11): 1938-49 inflammatory cytokines, specifically TNF , behavioral therapies and dependence who prefer sweets to education and prevention programs. β with human postmortem brains supplied by (2006). MCP-1, and IL-1 , in the brain; and loss psychosocial strategies to those who do not and their response the Australia Brain Donor Program, they Yes, I would like to join the effort to cure alcoholism in our lifetime. of neurons in the substantia nigra, a brain ensure medication compliance. to Naltrexone. Zou, J, Crews, FT. CREB and NF- observed neuroinflammation and increased region known to have lots of microglia. The program, part of UNC “These research efforts have been ___$50 ___$150 ___$250 ___$500 other _____ kappaB transcription factors regulate morphological signs of microglial activation. ASAP Staff (Left to Right): Ben Lancaster, LPC, Bill Renn, LCSW, sensitivity to excitotoxic and oxidative These experiments illustrate how Healthcare, the Bowles Center rewarding to the staff and have been ___$1000 Bowles Club ___$2000 Chancellor’s Club ___$5000 Dean’s Club Furthermore, they found that levels of the LCAS, Tom Watkins, LCAS, Arleta Brooks, CNA, Kathy Grace, LPC, stress induced neuronal cell death. inflammation originating outside the brain for Alcohol Studies and the J.C. Garbutt, MD. published in two major journals. Please return to: proinflammatory cytokine MCP-1 were __ Check enclosed, payable to the Bowles Center for Alcohol Studies Cell Mol Neurobiol, 26(4-6): 383-403 can trigger persistent brain inflammation Department of Psychiatry, specializes in individualized Although there are no medications dispensed or available at Bowles CAS significantly higher in the brains of __ My company matches gifts. The form is attached. (2006). that is associated with brain damage. treatment based on the unique needs, motivation and personal this clinic, our efforts led to the FDA approval of long-acting c/o Elizabeth Thomas α alcoholics than the brains of control, Elevated TNF in the periphery induced goals of each patient. injectable naltrexone for the treatment of alcohol dependence,” __ I would prefer to remain anonymous. Crews, FT, Bechara, R, Brown, LA, α moderate-drinking individuals. CB#7178, UNC-CH brain TNF , activated microglia, and “ASAP has the ability to treat individuals who need to said Renn. Guidot, DM, Mandrekar, P, Oak, S, Considered in aggregate, Crews’ findings Chapel Hill, NC 27599 Donations can also be made online through the Medical Foundation of NC at caused delayed neurodegeneration. “These commit to lifelong abstinence, as well as those patients who The Program is also heralding new initiatives that will make Qin, L, Szabo, G, Wheeler, M, Zou, J. α suggest that excessive alcohol consumption http://medicalfoundationofnc.org/donate.shtml Cytokines and alcohol. Alcohol Clin results suggest that when TNF is elevated are much more ambivalent about the damage that their alcohol treatment for patients even more convenient and accessible. sets off a spreading cytokine process Exp Res, 30(4): 720-30 (2006). in serum, the brain is also in trouble,” says or drug addiction is causing them,” said Bill Renn, ASAP In February, ASAP added a Day Treatment Group that meets (Figure). Alcohol disrupts cytokines both Crews. “One fascinating aspect of this Director and Associate Professor of Psychiatry at UNC. “Our four days a week, Monday through Thursday, from 1:30-3 within organs and between organs. For discovery is that serum cytokine levels models of care and our approaches are based on the latest p.m. The treatment sessions focus on a curriculum that Website example, alcohol perpetuates inflammation NAME E-MAIL ADDRESS return to normal, whereas the brain, once research and literature in the field, and I consider this to be a includes gaining and maintaining abstinence, relapse http://www.med.unc.edu/alcohol/ α within the brain when it induces NF-κB primed by serum TNF , has elevated national model for care based on the experience and expertise prevention, key coping and refusal skills, spirituality, ADDRESS CITY faculty/CrewsFT/Crews.htm DNA-binding activity, which activates proinflammatory cytokine levels for long of the staff.” meditation, and other science-based interventions. periods, perhaps forever.” inflammatory mediators that stimulate STATE AND COUNTRY ZIP/POSTAL CODE research alcohol actions on brain, liver, pancreas, fetus, the The Director’s Column endocrine system and the immune system, has contributed Thanks for your gifts to our Center! to Crews’ insights. Alternatively, I suspect that he A. Leslie Morrow, Ph.D. assembled this diverse group of researchers to study alcohol Dean Ms. Carolyn S. Corn Mr. and Mrs. Ben Madore Associate Director, actions across so many systems of the body for the very ’’’ s C Ms. Harriet W. Crisp Bowles Center for (annual gifts oflub $5000 and above) Ms. Regina J. Mahon purpose of discovering how the complex systemic and Mr. and Mrs. Ray Damerell Alcohol Studies Dr. William Maixner molecular roles of alcohol go awry in the disease of Center Line James A. Bowles Mr. Lewis A. Dancy Mrs. Melissa M. Mann Bowles Center for Alcohol Studies alcoholism. Mr. John N. Howard, Jr. Mr. F. E. Danielus Mr. and Mrs. H. J. McCarthy School of Medicine, University of North Carolina at Chapel Hill Mr. and Mrs. Robert F. Schaecher Mr. Stephen M. Dean and Ms. Patricia L. Ms. Michelle McCarthy This integration of research across systems, organs, brain Ms. Ann Lewallen Spencer Amend Mr. and Mrs. Robert H. McConville, Jr. Dr. Fulton Crews’ brilliance can be attributed in part to regions, human development and the progression to Our mission is to conduct, coordinate, and promote basic and clinical research on the causes, prevention, and treatment of alcoholism and alcoholic disease. Tennessee Medical Foundation Ms. Elizabeth L. Deaver Mr. and Mrs. Loyce L. McCormick his understanding that human beings are not just a alcoholism is the hallmark of research in the Bowles Center Ms. Patricia Delaney Ms. Patricia E. McEvoy conglomerate of molecules and cells but complex organisms for Alcohol Studies. Dr. Fulton Crews has led this Center Volume 18, Number 1, March 2007 Mr. Charles H. Dodson Mr. Todd B. Melet with integrated organ, immune and endocrine systems. to promote such integration and has brought together a Chancel Mr. and Mrs. Leonard P. Duevel Mr. Afshin Meymandi Crews Lab Discovers Inflammatory Mechanisms Underlying (annual gifts lorof $2000 - $4999) Mr. and Mrs. David R. Eaton Alcohol effects on all these systems will ultimately impact team of researchers determined to find the causes and ’’’ s Club Mr. William L. Mitchell Mr. Samuel P. Echeveste Dr. Sheryl S. Moy many molecules and cells throughout the body. Hence, successful treatments for alcoholism in our lifetime. Alcohol-Induced Brain Damage Dr. Fulton T. Crews Ms. Sandy E. Englebert-Johnson Mr. Richard Munich systemic effects of alcohol on the entire body play a role in The Crews Lab is likely to find how preventing the Dr. A. Leslie Morrow and Dr. Michael C. Lish Mr. Steven Erickson Ms. Noreen Ordronneau the ultimate effects of alcohol on brain cells – including the proinflammatory effects of alcohol can prevent the Mr. and Mrs. J. Glenn Thurman “I don’t drink these days. I am allergic research technology have made it body against infections. Anti- Ms. Jewell Everhart Mr. and Mrs. Thomas M. Osler ability of alcohol to kill brain cells. Perhaps leading the development of alcoholism and promote recovery by First United Methodist Church Cary, NC, Inc to alcohol.....I break out in handcuffs.” possible to study biological correlates of inflammatory cytokines and growth Dr. and Mrs. David H. Overstreet Bowles Center for Alcohol Studies, where investigators preventing relapse. His lab has shown that heavy alcohol Bo Mr. and Mrs. Louis D. Fitzgerald Mrs. Sharon B. Owens -Robert Downey, Jr. alcoholism. Dr. Fulton Crews, alcohol factors also contribute to the diverse wles C use can kill brain cells, prevent neurogenesis and the (annual gifts oflub $1000 - $1999) Dr. Rebekah L. Fleming Mr. Lester E. Pace While Robert Downey, actions of this large family Ms. Claire L. Flowers Mr. Edward F. Paquette The Bowles Center for survival of new brain cells, and promote inflammation Jr.’s statement was made in of mediators. Dr. James C. Garbutt Mr. and Mrs. Hargrove Bowles III Dr. and Mrs. Peter H. Patterson Alcohol Studies across organ systems that persists in the brain. jest, it encapsulates an Crews’ interest in Mr. Kirk J. Bradley Ms. Arline P. Gertzoff Mr. Robert A. Pearce and Mrs. Margaret M. Inflammation may be the key to many diseases in many Tel. (919) 966-5678 earnest opinion often cytokines was sparked by his Mr. Nathaniel T. Harris Gifford Family Foundation Pearce organs, as well as the endocrine and immune systems, that Mr. and Mrs. Gary Giles Fax. (919) 966-5679 expressed by alcoholics: Bowles Center colleagues’ Mr. James Kerrigan Ms. Sylvia D. Perry disrupts normal function and leads to the demise of the Mr. Gary W. Gillis that alcohol provokes an research demonstrating that Mr. and Mrs. Dennis R. Schaecher Mr. and Mrs. M. Randolph Phillips organism – the human being. Thus, the importance of Ms. Karen W. Watkins Mr. and Mrs. Eugene W. Goodwillie, Jr. Plan On It, Inv. “allergic reaction” tumor necrosis factor-α To become involved in our mission, call Crews’ research extends far beyond the effects of alcohol Dr. and Mrs. Jack L. Wilhelm Mr. and Mrs. Phillip E. Grace Ms. Eleanor R. Pohl Elizabeth Thomas at (919) 966-4977 or email characterized by a unique (TNFα), a proinflam- Mr. and Mrs. H. S. Willson in honor of Ms. Shara S. Graham Ms. Gail M. Poitras [email protected]. on brain cells and molecules. physiological and matory cytokine released by Ms. Elizabeth C. Grant Ms. Jo Carole Willson, MS, LPC, LCAS Dr. Karen S. Popovich and Mr. Kenneth S. Latta The faculty of the Bowles Center for Alcoholism, along psychological sensitivity to specific liver cells, Ms. Betsy C. Wright Mr. Frances Hall Ms. Erin N. Potts with their advisors and consultants recognized the Mr. and Mrs. Richard P. Hall alcohol’s effects. The idea contributes to liver disease Mr. and Mrs. H. W. Potts For treatment information call UNC Health achievements and brilliance of Fulton Crews by awarding Mr. Richard N. Hanes Care’s Alcohol and Substance Abuse Program that an allergic reaction to in alcoholism. Chronic Dr. Liya Qin Crews Lab (Left to Right): Front Row: Jian Zou, PhD, Richard Hanes, Jun He, Dr. Joseph M. Harmon at (919) 966-6039 or (888) 457-7457. him the 2006 Bowles Lectureship Award. We are proud Friends of the Center Mr. Gary Ramer alcohol underlies PhD, Fulton Crews, PhD, Liya Qin, PhD, Tonya Hurst, Olivera Pluzarev, PhD. alcohol use causes a leaky gut, Harris Incorporated Ms. Susan Reaney of his leadership of our Center, and we are proud to work alcoholism was first with bacteria and ethanol Anonymous Dr. Jun He Mr. William F. Renn, Jr. with a great coach towards the championship in the introduced into the medical literature by researcher and Director of the University combining to stimulate the liver to make Anonymous Mr. and Mrs. Richard G. Hiskey Mr. and Mrs. Jon David Richmond tournament to reduce human suffering from alcoholism. the New York physician W. D. of North Carolina’s Skipper Bowles TNFα and other cytokines as part of an Anonymous Dr. and Dr. C. W. Hodge Mr. and Mrs. Mike Riley www.med.unc.edu/alcohol Anonymous Mr. John N. Howard Mr. Daniel Rosen and Ms. Claudia J. Niles Silkworth. In his pioneering 1937 paper, Center for Alcohol Studies, is at the inflammatory reaction. Present in excess, α Mr. and Mrs. Lawrence D. Adcock Mr. Stuart Howard Ms. Sarah Safrit Center Line, Vol. 18, No. 1 Published quarterly to bring readers a greater understanding of alcoholism research and the Center’s mission. “Alcoholism as a Manifestation of forefront of efforts to elucidate the TNF and other cytokines cause cellular Mr. and Mrs. William R. Allen III Ms. Marilyn L. Huff Mr. and Mrs. George L. Schueppert A. Leslie Morrow, Ph.D., Editor-in-Chief; Elizabeth Thomas, Managing Editor; Jane Saiers, Ph.D., Science Writer Allergy,” Silkworth argued that neurobiology of alcoholism. Crews says toxicity and over time contribute to Mr. and Mrs. Michael R. Amend Ms. Beth Ann Huskamp Ms. Angela Sercer alcoholism is a physical malady with a that, while Silkworth’s concept of alcoholic liver disease. Crews, whose Mr. and Mrs. G. E. Barnes Mr. and Mrs. Doug Hutchins Mr. J. Lansing Smith UNC Bowles Center for Alcohol Studies Non-Profit Organization development and course analogous in alcoholism as a classical allergic reaction primary research focus is alcohol- Ms. Helen J. Benson Mr. and Mrs. William M. Iacuessa Mr. and Mrs. Ralph N. Smith CB# 7178, Thurston-Bowles Building US Postage many respects to allergies such as hay has not been fully supported, remarkable induced brain degeneration, speculated Dr. Wilbert W. Blackman Mr. Jon Irish and Mrs. Janet Head Ms. Rhonda Steele 5 PAID Mr. and Mrs. William M. Borndahl Mr. Thomas H. Jewett Mr. and Mrs. Jack M. Streb University of North Carolina at Chapel Hill Permit No. 177 fever. His conceptualization of parallels between allergic responses and that cytokines might also contribute to Mr. and Mrs. Erskine B. Bowles Mr. and Mrs. Roger L. Johnson Ms. Rory M. Taylor Chapel Hill, North Carolina 27599-7178 Chapel Hill, NC 27599-1800 alcoholism as an allergic state ran the body’s response to alcohol have been neurodegeneration in alcoholism. Ms. Roxanne J. Boyd Mr. Daniel H. Kim Mrs. Alice W. Thomason counter to the prevailing view of revealed. In short, both allergic Cytokines are produced in the brain by Mr. and Mrs. Richard H. Bradford Dr. Darin J. Knapp and Dr. Jane Saiers Mr. and Mrs. C. Duke Thompson alcoholism as a moral failing and responses and the body’s response to microglia, which are the brain’s immune Mr. and Mrs. Gerald L. Brown Mr. Mong Kong Ms. Sarah K. Tiller continues to resonate among today’s alcohol involve inflammatory processes cells. In a study in rats, Crews and his Mr. and Mrs. David W. Buck Dr. Marcia A. Koomen Mr. and Mrs. Stephen G. Toigo alcoholics and recovering alcoholics, who in which cytokines play key roles. colleagues discovered that a binge Ms. Jacquelyn G. Burgess Dr. Sandeep Kumar and Dr. Himi Saxena Mr. and Mrs. Lane VanderHoek Ms. Erin Burk-Tappy Ms. Mary A. Lambert Mr. Frans L. Victorson still widely cite and discuss Silkworth’s Cytokines constitute a diverse group of alcohol treatment regimen modeling the Mr. and Mrs. J. Brian Butler Mr. Benajmin M. Lancaster, Jr Mrs. Maureen Vollmer work. proteins that regulate immune drinking pattern of human alcoholics in Ms. Kimberley J. Campbell Ms. Edmonia L. Lang Ms. Walker G. Weigel In the 1930s, before the advent of responses, inflammation, hormones, fact caused microglial activation Ms. Michelle Carter Mr. Brian Lapham and Dr. Donita Robinson Mr. and Mrs. Thomas W. Whisnant neurobiological research on alcohol wound healing, and communication accompanied by persistent increases in Mr. Michael L. Case Ms. Doris L. Lee Mr. and Mrs. Paul S. Wilcox effects, Silkworth had no means of among cells throughout the body. Only the proinflammatory cytokines TNFα, Mr. and Mrs. Taylor M. Chambers Mr. Bernard Leewood Ms. M. E. Wilkie garnering biological support for his recently have they been studied in the interleukin-1 beta (IL-1β), and Mr. and Mrs. Elliot Chase Dr. Joan Lenowitz Mr. and Mrs. David C. Wright Ms. Marie W. B. Cherry Ms. Vicky Lepoutre Mr. and Mrs. Norman A. Wulf hypothesis of alcoholism as an allergic brain. The action of pro-inflammatory monocyte chemotactic protein-1 Mr. and Mrs. H. J. Cobb Mr. Johnathan Lorencz Dr. Jian Y. Zou reaction. Subsequent advances in cytokines is crucial for defending the (MCP-1). These cytokine changes were Ms. Meghan W. Cody This document is supported by subscriptions and donations to the Bowles Center for Alcohol Studies; All research partially funded by NIAAA. Ms. Shirlyn R. MacPherson Continued on next page research alcohol actions on brain, liver, pancreas, fetus, the The Director’s Column endocrine system and the immune system, has contributed Thanks for your gifts to our Center! to Crews’ insights. Alternatively, I suspect that he A. Leslie Morrow, Ph.D. assembled this diverse group of researchers to study alcohol Dean Ms. Carolyn S. Corn Mr. and Mrs. Ben Madore Associate Director, actions across so many systems of the body for the very ’’’ s C Ms. Harriet W. Crisp Bowles Center for (annual gifts oflub $5000 and above) Ms. Regina J. Mahon purpose of discovering how the complex systemic and Mr. and Mrs. Ray Damerell Alcohol Studies Dr. William Maixner molecular roles of alcohol go awry in the disease of Center Line James A. Bowles Mr. Lewis A. Dancy Mrs. Melissa M. Mann Bowles Center for Alcohol Studies alcoholism. Mr. John N. Howard, Jr. Mr. F. E. Danielus Mr. and Mrs. H. J. McCarthy School of Medicine, University of North Carolina at Chapel Hill Mr. and Mrs. Robert F. Schaecher Mr. Stephen M. Dean and Ms. Patricia L. Ms. Michelle McCarthy This integration of research across systems, organs, brain Ms. Ann Lewallen Spencer Amend Mr. and Mrs. Robert H. McConville, Jr. Dr. Fulton Crews’ brilliance can be attributed in part to regions, human development and the progression to Our mission is to conduct, coordinate, and promote basic and clinical research on the causes, prevention, and treatment of alcoholism and alcoholic disease. Tennessee Medical Foundation Ms. Elizabeth L. Deaver Mr. and Mrs. Loyce L. McCormick his understanding that human beings are not just a alcoholism is the hallmark of research in the Bowles Center Ms. Patricia Delaney Ms. Patricia E. McEvoy conglomerate of molecules and cells but complex organisms for Alcohol Studies. Dr. Fulton Crews has led this Center Volume 18, Number 1, March 2007 Mr. Charles H. Dodson Mr. Todd B. Melet with integrated organ, immune and endocrine systems. to promote such integration and has brought together a Chancel Mr. and Mrs. Leonard P. Duevel Mr. Afshin Meymandi Crews Lab Discovers Inflammatory Mechanisms Underlying (annual gifts lorof $2000 - $4999) Mr. and Mrs. David R. Eaton Alcohol effects on all these systems will ultimately impact team of researchers determined to find the causes and ’’’ s Club Mr. William L. Mitchell Mr. Samuel P. Echeveste Dr. Sheryl S. Moy many molecules and cells throughout the body. Hence, successful treatments for alcoholism in our lifetime. Alcohol-Induced Brain Damage Dr. Fulton T. Crews Ms. Sandy E. Englebert-Johnson Mr. Richard Munich systemic effects of alcohol on the entire body play a role in The Crews Lab is likely to find how preventing the Dr. A. Leslie Morrow and Dr. Michael C. Lish Mr. Steven Erickson Ms. Noreen Ordronneau the ultimate effects of alcohol on brain cells – including the proinflammatory effects of alcohol can prevent the Mr. and Mrs. J. Glenn Thurman “I don’t drink these days. I am allergic research technology have made it body against infections. Anti- Ms. Jewell Everhart Mr. and Mrs. Thomas M. Osler ability of alcohol to kill brain cells. Perhaps leading the development of alcoholism and promote recovery by First United Methodist Church Cary, NC, Inc to alcohol.....I break out in handcuffs.” possible to study biological correlates of inflammatory cytokines and growth Dr. and Mrs. David H. Overstreet Bowles Center for Alcohol Studies, where investigators preventing relapse. His lab has shown that heavy alcohol Bo Mr. and Mrs. Louis D. Fitzgerald Mrs. Sharon B. Owens -Robert Downey, Jr. alcoholism. Dr. Fulton Crews, alcohol factors also contribute to the diverse wles C use can kill brain cells, prevent neurogenesis and the (annual gifts oflub $1000 - $1999) Dr. Rebekah L. Fleming Mr. Lester E. Pace While Robert Downey, actions of this large family Ms. Claire L. Flowers Mr. Edward F. Paquette The Bowles Center for survival of new brain cells, and promote inflammation Jr.’s statement was made in of mediators. Dr. James C. Garbutt Mr. and Mrs. Hargrove Bowles III Dr. and Mrs. Peter H. Patterson Alcohol Studies across organ systems that persists in the brain. jest, it encapsulates an Crews’ interest in Mr. Kirk J. Bradley Ms. Arline P. Gertzoff Mr. Robert A. Pearce and Mrs. Margaret M. Inflammation may be the key to many diseases in many Tel. (919) 966-5678 earnest opinion often cytokines was sparked by his Mr. Nathaniel T. Harris Gifford Family Foundation Pearce organs, as well as the endocrine and immune systems, that Mr. and Mrs. Gary Giles Fax. (919) 966-5679 expressed by alcoholics: Bowles Center colleagues’ Mr. James Kerrigan Ms. Sylvia D. Perry disrupts normal function and leads to the demise of the Mr. Gary W. Gillis that alcohol provokes an research demonstrating that Mr. and Mrs. Dennis R. Schaecher Mr. and Mrs. M. Randolph Phillips organism – the human being. Thus, the importance of Ms. Karen W. Watkins Mr. and Mrs. Eugene W. Goodwillie, Jr. Plan On It, Inv. “allergic reaction” tumor necrosis factor-α To become involved in our mission, call Crews’ research extends far beyond the effects of alcohol Dr. and Mrs. Jack L. Wilhelm Mr. and Mrs. Phillip E. Grace Ms. Eleanor R. Pohl Elizabeth Thomas at (919) 966-4977 or email characterized by a unique (TNFα), a proinflam- Mr. and Mrs. H. S. Willson in honor of Ms. Shara S. Graham Ms. Gail M. Poitras [email protected]. on brain cells and molecules. physiological and matory cytokine released by Ms. Elizabeth C. Grant Ms. Jo Carole Willson, MS, LPC, LCAS Dr. Karen S. Popovich and Mr. Kenneth S. Latta The faculty of the Bowles Center for Alcoholism, along psychological sensitivity to specific liver cells, Ms. Betsy C. Wright Mr. Frances Hall Ms. Erin N. Potts with their advisors and consultants recognized the Mr. and Mrs. Richard P. Hall alcohol’s effects. The idea contributes to liver disease Mr. and Mrs. H. W. Potts For treatment information call UNC Health achievements and brilliance of Fulton Crews by awarding Mr. Richard N. Hanes Care’s Alcohol and Substance Abuse Program that an allergic reaction to in alcoholism. Chronic Dr. Liya Qin Crews Lab (Left to Right): Front Row: Jian Zou, PhD, Richard Hanes, Jun He, Dr. Joseph M. Harmon at (919) 966-6039 or (888) 457-7457. him the 2006 Bowles Lectureship Award. We are proud Friends of the Center Mr. Gary Ramer alcohol underlies PhD, Fulton Crews, PhD, Liya Qin, PhD, Tonya Hurst, Olivera Pluzarev, PhD. alcohol use causes a leaky gut, Harris Incorporated Ms. Susan Reaney of his leadership of our Center, and we are proud to work alcoholism was first with bacteria and ethanol Anonymous Dr. Jun He Mr. William F. Renn, Jr. with a great coach towards the championship in the introduced into the medical literature by researcher and Director of the University combining to stimulate the liver to make Anonymous Mr. and Mrs. Richard G. Hiskey Mr. and Mrs. Jon David Richmond tournament to reduce human suffering from alcoholism. the New York physician W. D. of North Carolina’s Skipper Bowles TNFα and other cytokines as part of an Anonymous Dr. and Dr. C. W. Hodge Mr. and Mrs. Mike Riley www.med.unc.edu/alcohol Anonymous Mr. John N. Howard Mr. Daniel Rosen and Ms. Claudia J. Niles Silkworth. In his pioneering 1937 paper, Center for Alcohol Studies, is at the inflammatory reaction. Present in excess, α Mr. and Mrs. Lawrence D. Adcock Mr. Stuart Howard Ms. Sarah Safrit Center Line, Vol. 18, No. 1 Published quarterly to bring readers a greater understanding of alcoholism research and the Center’s mission. “Alcoholism as a Manifestation of forefront of efforts to elucidate the TNF and other cytokines cause cellular Mr. and Mrs. William R. Allen III Ms. Marilyn L. Huff Mr. and Mrs. George L. Schueppert A. Leslie Morrow, Ph.D., Editor-in-Chief; Elizabeth Thomas, Managing Editor; Jane Saiers, Ph.D., Science Writer Allergy,” Silkworth argued that neurobiology of alcoholism. Crews says toxicity and over time contribute to Mr. and Mrs. Michael R. Amend Ms. Beth Ann Huskamp Ms. Angela Sercer alcoholism is a physical malady with a that, while Silkworth’s concept of alcoholic liver disease. Crews, whose Mr. and Mrs. G. E. Barnes Mr. and Mrs. Doug Hutchins Mr. J. Lansing Smith UNC Bowles Center for Alcohol Studies Non-Profit Organization development and course analogous in alcoholism as a classical allergic reaction primary research focus is alcohol- Ms. Helen J. Benson Mr. and Mrs. William M. Iacuessa Mr. and Mrs. Ralph N. Smith CB# 7178, Thurston-Bowles Building US Postage many respects to allergies such as hay has not been fully supported, remarkable induced brain degeneration, speculated Dr. Wilbert W. Blackman Mr. Jon Irish and Mrs. Janet Head Ms. Rhonda Steele 5 PAID Mr. and Mrs. William M. Borndahl Mr. Thomas H. Jewett Mr. and Mrs. Jack M. Streb University of North Carolina at Chapel Hill Permit No. 177 fever. His conceptualization of parallels between allergic responses and that cytokines might also contribute to Mr. and Mrs. Erskine B. Bowles Mr. and Mrs. Roger L. Johnson Ms. Rory M. Taylor Chapel Hill, North Carolina 27599-7178 Chapel Hill, NC 27599-1800 alcoholism as an allergic state ran the body’s response to alcohol have been neurodegeneration in alcoholism. Ms. Roxanne J. Boyd Mr. Daniel H. Kim Mrs. Alice W. Thomason counter to the prevailing view of revealed. In short, both allergic Cytokines are produced in the brain by Mr. and Mrs. Richard H. Bradford Dr. Darin J. Knapp and Dr. Jane Saiers Mr. and Mrs. C. Duke Thompson alcoholism as a moral failing and responses and the body’s response to microglia, which are the brain’s immune Mr. and Mrs. Gerald L. Brown Mr. Mong Kong Ms. Sarah K. Tiller continues to resonate among today’s alcohol involve inflammatory processes cells. In a study in rats, Crews and his Mr. and Mrs. David W. Buck Dr. Marcia A. Koomen Mr. and Mrs. Stephen G. Toigo alcoholics and recovering alcoholics, who in which cytokines play key roles. colleagues discovered that a binge Ms. Jacquelyn G. Burgess Dr. Sandeep Kumar and Dr. Himi Saxena Mr. and Mrs. Lane VanderHoek Ms. Erin Burk-Tappy Ms. Mary A. Lambert Mr. Frans L. Victorson still widely cite and discuss Silkworth’s Cytokines constitute a diverse group of alcohol treatment regimen modeling the Mr. and Mrs. J. Brian Butler Mr. Benajmin M. Lancaster, Jr Mrs. Maureen Vollmer work. proteins that regulate immune drinking pattern of human alcoholics in Ms. Kimberley J. Campbell Ms. Edmonia L. Lang Ms. Walker G. Weigel In the 1930s, before the advent of responses, inflammation, hormones, fact caused microglial activation Ms. Michelle Carter Mr. Brian Lapham and Dr. Donita Robinson Mr. and Mrs. Thomas W. Whisnant neurobiological research on alcohol wound healing, and communication accompanied by persistent increases in Mr. Michael L. Case Ms. Doris L. Lee Mr. and Mrs. Paul S. Wilcox effects, Silkworth had no means of among cells throughout the body. Only the proinflammatory cytokines TNFα, Mr. and Mrs. Taylor M. Chambers Mr. Bernard Leewood Ms. M. E. Wilkie garnering biological support for his recently have they been studied in the interleukin-1 beta (IL-1β), and Mr. and Mrs. Elliot Chase Dr. Joan Lenowitz Mr. and Mrs. David C. Wright Ms. Marie W. B. Cherry Ms. Vicky Lepoutre Mr. and Mrs. Norman A. Wulf hypothesis of alcoholism as an allergic brain. The action of pro-inflammatory monocyte chemotactic protein-1 Mr. and Mrs. H. J. Cobb Mr. Johnathan Lorencz Dr. Jian Y. Zou reaction. Subsequent advances in cytokines is crucial for defending the (MCP-1). These cytokine changes were Ms. Meghan W. Cody This document is supported by subscriptions and donations to the Bowles Center for Alcohol Studies; All research partially funded by NIAAA. Ms. Shirlyn R. MacPherson Continued on next page