DOCSLIB.ORG

Evidence for Systemic Immune System Alterations in Sporadic Amyotrophic Lateral Sclerosis (Sals)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Evidence for Systemic Immune System Alterations in Sporadic Amyotrophic Lateral Sclerosis (Sals) Journal of Neuroimmunology 159 (2005) 215–224 www.elsevier.com/locate/jneuroim Evidence for systemic immune system alterations in sporadic amyotrophic lateral sclerosis (sALS) Rongzhen Zhanga, Ron Gascona, Robert G. Millerb, Deborah F. Gelinasb, Jason Massb, Ken Hadlockc, Xia Jinc, Jeremy Reisa, Amy Narvaeza, Michael S. McGratha,* aUniversity of California, San Francisco, San Francisco General Hospital, 995 Potrero Avenue, Building 80, Ward 84, Box 0874, San Francisco, CA 94110, USA bCalifornia Pacific Medical Center, San Francisco, CA 94115, USA cPathologica LLC, Burlingame, CA 94010, USA Received 12 February 2004; received in revised form 7 September 2004; accepted 12 October 2004 Abstract Sporadic amyotrophic lateral sclerosis (sALS) is a progressive neuroinflammatory disease of spinal cord motor neurons of unclear etiology. Blood from 38 patients with sALS, 28 aged-match controls, and 25 Alzheimer’s disease (AD) patients were evaluated and activated monocyte/macrophages were observed in all patients with sALS and AD; the degree of activation was directly related to the rate of sALS disease progression. Other parameters of T-cell activation and immune globulin levels showed similar disease associated changes. These data are consistent with a disease model previously suggested for AD, wherein systemic immunologic activation plays an active role in sALS. D 2004 Elsevier B.V. All rights reserved. Keywords: Amyotrophic lateral sclerosis (ALS); Alzheimer’s disease (AD); Motor neuron disease; Immune activation; Monocyte/macrophage 1. Introduction 1995; Fray et al., 1998), and autoimmunity (Appel et al., 1993). In addition, several recent studies have suggested Amyotrophic lateral sclerosis (ALS) is a devastating that the immune system may be actively involved in the neurological disease characterized by gradual degeneration disease process of ALS, with observations of activated of spinal cord motor neuron cells leading to progressive microglia, IgG deposits, and dysregulation of cytokine weakness, paralysis of muscle and death. Almost 90% of expression in the spinal cord of ALS patients (Troost et ALS patients are characterized as having sporadic ALS al., 1989; Engelhardt and Appel, 1990; Schiffer et al., 1996; (sALS) with 10% having a familial form, a subset of whom Hayashi et al., 2001). However, despite intensive inves- have point mutations in their superoxide dismutase (SOD) tigation ALS has no known cause or effective therapy. gene. The pathogenesis of ALS is incompletely understood, Inflammatory mechanisms and immune reactivity have although different hypotheses have been suggested, includ- been hypothesized to play a role in the pathogeneses of ing mitochondria dysfunction (Richter et al., 1988; Wong et central nervous system (CNS) disease (Akiyama et al., al., 1995; Curti et al., 1996), mutation in the superoxide 2000; Minagar et al., 2002; Bar-Or et al., 2003; Filion et al., dismutase gene (Deng et al., 1993; Durham et al., 1997), 2003, Hirsch et al., 2003; Floris et al., 2004; Ringheim and defects in neuronal glutamate transports (Rothstein et al., Conant, 2004), including ALS (Alexianu et al., 2001; McGeer and McGeer, 2002; Henkel et al., 2004; Simpson et al., 2004). Furthermore, various studies have suggested * Corresponding author. Tel.: +1 415 476 4082x415; fax: +1 415 476 that monocyte/macrophage activation may play a significant 6017. role in the pathogenesis of many neurological diseases, such E-mail address: [email protected] (M.S. McGrath). as Alzheimer’s disease (AD) (Smits et al., 2000; Fiala et al., 0165-5728/$ - see front matter D 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.jneuroim.2004.10.009 216 R. Zhang et al. / Journal of Neuroimmunology 159 (2005) 215–224 2002), multiple sclerosis (MS) (Minagar et al., 2002; Filion criteria (Brooks, 1994) at the Forbes Norris MDA/ALS et al., 2003), Parkinson’s disease (McGeer et al., 1988), and Research Center (San Francisco, CA, USA) had blood HIV-associated dementia (HAD) (Pulliam et al., 1997; drawn in accordance with the CPMC (California Pacific Diesing et al., 2002). Indeed, the best pathological correlate Medical Center) and UCSF committees on human research for HIV-associated neurologic disorders, especially HAD, is guidelines, coordinated by the UCSF AIDS and Cancer the number of activated mononuclear phagocytes present in Specimen Resource (ACSR) program. The Revised ALS the brain (perivascular and parenchymal blood-derived Functional Rating Scale (ALSFRS-R), scored 0–48, was macrophages and microglia), and not the absolute level of used to evaluate overall patient functional status (Cedar- HIV in the brain (Glass et al., 1995; Adamson et al., 1999). baum et al., 1999). All scores were updated within a month Similar findings have been reported for simian AIDS related of blood testing. Patients had sALS for 4–93 months with a encephalopathy (SIVE) (Williams et al., 2002). Studies on range of ALSFRS-R scores of 8–43. Demographic infor- blood from patients with HAD (Liu et al., 2000) and mation on sALS patients whose specimens were studied is monkeys with SIVE (Williams et al., 2002) have shown a shown in Table 1, in which 12 patients were using various direct relationship between the presence of activated blood anti-inflammatory medications with standard dose (Cele- macrophages and CNS disease. These activated macro- brex, Vioxx, Naproxyn, Excedrin), and 30 patients were phages are thought to mediate blood–brain barrier (BBB) taking riluzole (50 mg twice daily); 10 patients received breakdown and directly contribute to CNS pathogenesis. both medications. Given evidence of macrophage activation in spinal cords of Two control groups were used in the study. The first patients with ALS disease (Engelhardt and Appel, 1990; control group consisted of 28 age-matched normal blood Appel et al., 1993; Obal et al., 2001; McGeer and McGeer, samples (10 females and 18 males, mean age 56.0F15.1 2002; Wilms et al., 2003; Henkel et al., 2004), a pathogenic years), which were obtained from blood draws at Stanford process similar to these may occur in ALS. University Blood Center and processed in a similar manner In addition to local evidence for tissue associated to the sALS patient blood specimens. Normal control macrophage activation, increasing numbers of studies on samples for IgG and IgM studies consisted of plasma from peripheral immune activation levels in CNS disease patients 80 blood donors and were also obtained from the Stanford such as AD (Shalit et al., 1995; Scali et al., 2002; Casal et University Blood Center. The second control group obtained al., 2003), HIV-associated neurologic disorder (Pulliam et from the same source as sALS, had Alzheimer’s disease al., 1997; Sanchez-Ramon et al., 2003) and MS (Bar-Or et (AD). This group consisted of 25 AD patients (11 females al., 2003; Filion et al., 2003) support the hypothesis of a and 14 males, mean age 77.5F7.9), and was used as peripheral immune reaction which might be correlated with neurological disease controls. the clinical stages of disease. In order to examine whether macrophage activation observed in spinal cords of ALS 2.2. Flow cytometry patients would be reflected in the systemic immune system, the current study was designed: (1) to detect differences, if About 10 ml of peripheral blood was drawn from each any, in the expression of monocyte/macrophage and T-cell patient and normal controls into heparinized tubes and activation markers in peripheral blood mononuclear cells transferred to the laboratory at room temperature for same (PBMC) between sALS patients and controls and (2) to test day immunologic studies. Cellular immunologic activation whether the peripheral immune activation state in sALS was evaluated by quantitating levels of CD38 on T-cell patient blood would correlate with clinical stage of disease. subsets and HLA-DR on CD14 cells. CD16 (Fc gamma III This study shows for the first time that the pattern of receptor) expression on CD14 cells was used as another immunologic activation in blood cells from patients with marker for monocyte differentiation and has been an antigen sALS correlates with ALS disease state and that rate of associated with cytokine expression patterns characteristic disease progression is directly related to the degree of of tissue macrophages (Ziegler-Heitbrock et al., 1993; systemic monocyte/macrophage activation. These data are Frankenberger et al., 1996). The monocyte granularity consistent with a model of sALS that includes systemic associated with its differentiation was measured by CD14- immunologic dysfunction as a cofactor in disease patho- associated bbackgatingQ on side light-scatter characteristics genesis, not dissimilar to pathogenic models for AD, MS (SSC). Whole blood was stained with CD14-fluorescein and HAD as described above. isothiocyanate (FITC), CD16-phycoerythrin (PE) (DAKO, Carpinteria, CA, USA), CD8-FITC, CD38-PE, HLA-DR- PE, and CD4-peridinin chlorophyll protein (PerCP) (Bec- 2. Methods ton-Dickinson, San Jose, CA, USA) for 15 min at room temperature. Negative controls consisted of aliquots stained 2.1. Subjects with isotype IgG-FITC, IgG-PE, and IgG-PerCP; all staining was performed as per manufacturers specifications. Thirty-eight patients diagnosed with sALS (12 females Samples were then lysed with FACS Lysing Solution and 26 males, mean age 59.3F13.4 years) by El Escorial (Becton-Dickinson) for 10 min at room temperature R. Zhang et al. / Journal of Neuroimmunology 159 (2005) 215–224 217 Table 1 Clinical summary of sALS
Load more

Recommended publications
  • Advances in Dental Research
    Advances in Dental Research http://adr.sagepub.com/ The Association Between Immunodeficiency and the Development of Autoimmune Disease J.W. Sleasman ADR 1996 10: 57 DOI: 10.1177/08959374960100011101 The online version of this article can be found at: http://adr.sagepub.com/content/10/1/57 Published by: http://www.sagepublications.com On behalf of: International and American Associations for Dental Research Additional services and information for Advances in Dental Research can be found at: Email Alerts: http://adr.sagepub.com/cgi/alerts Subscriptions: http://adr.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav Downloaded from adr.sagepub.com by guest on July 18, 2011 For personal use only. No other uses without permission. THE ASSOCIATION BETWEEN IMMUNODEFICIENCY AND THE DEVELOPMENT OF AUTOIMMUNE DISEASE J.W. SLEASMAN aradoxically, individuals with primary or acquired immunodeficiency disease have an increased Division of Pediatric Immunology and Allergy incidence of autoimmunity. Human primary University of Florida College of Medicine immunodeficiency disease can be classified as Box 100296, 1600 SW Archer Road P disorders of cell-mediated immunity, humoral immunity, Gainesville, Florida 32610-0296 phagocytic cell function, and the complement system (Barrett and Sleasman, 1990). Cell-mediated and humoral immunity Adv Dent Res 10(l):57-61, April, 1996 comprise the adaptive arm of the immune response, which is antigen-specific and confers immunologic memory. The innate immune response, which is antigen-nonspecific, is Abstract—There is a paradoxical relationship between composed of phagocytic cells and the inflammatory peptides. immunodeficiency diseases and autoimmunity. While not all Not all individuals with inherited immunodeficiency develop individuals with immunodeficiency develop autoimmunity, autoimmunity, nor are all individuals with autoimmune nor are all individuals with autoimmunity immunodeficient, disease immunodeficient.
    [Show full text]
  • Immune Checkpoint Blockade in Cancer Therapy Michael A
    Published Ahead of Print on January 20, 2015 as 10.1200/JCO.2014.59.4358 The latest version is at http://jco.ascopubs.org/cgi/doi/10.1200/JCO.2014.59.4358 JOURNAL OF CLINICAL ONCOLOGY REVIEW ARTICLE Immune Checkpoint Blockade in Cancer Therapy Michael A. Postow, Margaret K. Callahan, and Jedd D. Wolchok All authors: Memorial Sloan Kettering Cancer Center and Weill Cornell Medi- ABSTRACT cal College, New York, NY. Immunologic checkpoint blockade with antibodies that target cytotoxic T lymphocyte–associated Published online ahead of print at www.jco.org on January 20, 2015. antigen 4 (CTLA-4) and the programmed cell death protein 1 pathway (PD-1/PD-L1) have demonstrated promise in a variety of malignancies. Ipilimumab (CTLA-4) and pembrolizumab Authors’ disclosures of potential (PD-1) are approved by the US Food and Drug Administration for the treatment of advanced conflicts of interest are found in the article online at www.jco.org. Author melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a contributions are found at the end of variety of other agents that target these pathways. Treatment with both CTLA-4 and PD-1/PD-L1 this article. blockade is associated with a unique pattern of adverse events called immune-related adverse Corresponding author: Jedd D. events, and occasionally, unusual kinetics of tumor response are seen. Combination approaches Wolchok, MD, PhD, Memorial Sloan involving CTLA-4 and PD-1/PD-L1 blockade are being investigated to determine whether they Kettering, Cancer Center, 1275 York enhance the efficacy of either approach alone.
    [Show full text]
  • Model-Based Inference and Classification of Immunologic Control Mechanisms from TKI Cessation and Dose Reduction in Patients with CML
    Published OnlineFirst February 10, 2020; DOI: 10.1158/0008-5472.CAN-19-2175 CANCER RESEARCH | CONVERGENCE AND TECHNOLOGIES Model-Based Inference and Classification of Immunologic Control Mechanisms from TKI Cessation and Dose Reduction in Patients with CML Tom Hahnel€ 1, Christoph Baldow1,Joelle€ Guilhot2, Francois¸ Guilhot2, Susanne Saussele3, Satu Mustjoki4,5, Stefanie Jilg6, Philipp J. Jost6, Stephanie Dulucq7, Francois-Xavier¸ Mahon8, Ingo Roeder1,9, Artur C. Fassoni10, and Ingmar Glauche1 ABSTRACT ◥ Recent clinicalfindings in patients with chronic myeloid leukemia a third class of patients that maintained TFR only if an optimal (CML) suggest that the risk of molecular recurrence after stopping balance between leukemia abundance and immunologic activation tyrosine kinase inhibitor (TKI) treatment substantially depends on was achieved before treatment cessation. Model simulations further an individual's leukemia-specific immune response. However, it is suggested that changes in the BCR-ABL1 dynamics resulting from still not possible to prospectively identify patients that will remain in TKI dose reduction convey information about the patient-specific treatment-free remission (TFR). Here, we used an ordinary differ- immune system and allow prediction of outcome after treatment ential equation model for CML, which explicitly includes an cessation. This inference of individual immunologic configurations antileukemic immunologic effect, and applied it to 21 patients with based on treatment alterations can also be applied to other cancer CML for whom BCR-ABL1/ABL1 time courses had been quantified types in which the endogenous immune system supports mainte- before and after TKI cessation. Immunologic control was concep- nance therapy, long-term disease control, or even cure. tually necessary to explain TFR as observed in about half of the patients.
    [Show full text]
  • Paradoxical Effects of Brain Death and Associated Trauma on Rat Mesenteric Microcirculation: an Intravital Microscopic Study
    CLINICS 2012;67(1):69-75 DOI:10.6061/clinics/2012(01)11 BASIC RESEARCH Paradoxical effects of brain death and associated trauma on rat mesenteric microcirculation: an intravital microscopic study Rafael Simas, Paulina Sannomiya, Jose´ Walber M. C. Cruz, Cristiano de Jesus Correia, Fernando Luiz Zanoni, Maurı´cio Kase, Laura Menegat, Isaac Azevedo Silva, Luiz Felipe P. Moreira Faculdade de Medicina da Universidade de Sa˜ o Paulo, Instituto do Corac¸a˜ o (InCor), Laborato´ rio de Cirurgia Cardiovascular e Fisiopatologia da Circulac¸a˜o, Sa˜ o Paulo/SP, Brazil. OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death–associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of P- selectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals.
    [Show full text]
  • Interferon Regulatory Factor 8 Integrates T-Cell Receptor and Cytokine-Signaling Pathways and Drives Effector Differentiation of CD8 T Cells
    Interferon regulatory factor 8 integrates T-cell receptor and cytokine-signaling pathways and drives effector differentiation of CD8 T cells Fumi Miyagawaa, Hong Zhanga, Atshushi Terunumaa, Keiko Ozatob, Yutaka Tagayac,1,2,3, and Stephen I. Katza,1,3 aDermatology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; bLaboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892; and cMetabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 Edited* by Thomas A. Waldmann, National Cancer Institute, National Institutes of Health, Bethesda, MD, and approved June 19, 2012 (received for review January 26, 2012) We recently demonstrated that differentiation of cytotoxic T cells differentiation (27). Nevertheless, the role of IRF8 in CD8 T requires cooperation between T-cell receptor (TCR)/costimulation cells remains elusive; IRF8KO mice manifest impaired CD8 and γc-cytokines. Here we demonstrate that the transcription fac- T-cell responses against certain viruses (22). Thus, we embarked tor IFN regulatory factor 8 (IRF8) is expressed in CD8 T cells by the on a detailed assessment of the role of IRF8 in CD8 T cells. Here, we demonstrate the critical need for the convergence of combination of these two signals. More importantly, depletion of γ IRF8 in these cells abrogated the differentiation of naive CD8 T cells c-Jak3 and TCR/costimulation-signaling pathways in the tran- scription of IRF8 and demonstrate that removal of IRF8 cripples into effector cells in an experimental graft-vs.-host disease mouse fi − model.
    [Show full text]
  • Table of Contents (PDF)
    139 (5) J Immunol 1987; 139:1379-1746; ; http://www.jimmunol.org/content/139/5.citation This information is current as of October 1, 2021. Downloaded from Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists http://www.jimmunol.org/ • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: by guest on October 1, 2021 http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. THE JOURNAL OF IMMUNOLOGY Volume 139/Number 5, September 1, 1987 Contents CELLULAR IMMUNOLOGY E. B. Bell, S. M. Sparshott, M. 1379 The Stable and Permanent Expansion of Functional T Lymphocytes in T. Drayson. and W. L. Ford Athymic Nude Rats aftera Single Injection of Mature T Cells P. A. Campbell, J. M. Collins, 1385 A Spleen-Derived Maturational Factor Allows Immature Thymocytes, Pre- and K. E. Stedman pared as Cells Bearing Low Amounts of Surface Sialic Acid, to Become Cytotoxic T Cells N. Kumagai. S. H. Benedict, G. 1393 Requirements for the Simultaneous Presenceof Phorbol Esters andCalcium B. Mills, and E. W.Gelfand Ionophores in the Expression of Human T Lymphocyte Proliferation Re- lated Genes A.
    [Show full text]
  • Immunological Profiling of Obesity
    Journal of Vol. 4, No. 1, 1-7 Lifestyle Review Article http://dx.doi.org/10.15280/jlm.2014.4.1.1 Medicine Immunological Profiling of Obesity Rosa Mistica C. Ignacio1, Cheol-Su Kim2, Soo-Ki Kim2,3,* 1Department of Environmental Medical Biology, 2Department of Microbiology, and 3Institute of Lifestyle Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea It is widely accepted that chronic inflammation contributes to the pathogenesis of obesity. Researchers have recently discovered that increased inflammatory cytokines and the infiltration and activation of macrophage cells in the adipose tissue are related to chronic obesity. This immunologic dysregulation has led to the development of the classical pro-in- flammatory paradigm. However, since chronic inflammation associated with obesity is more than just the over- production of pro-inflammatory cytokines, precise dissection requires beyond the classical pro-inflammatory cytokines. The purpose of this review is to summarize the immunological profiling of obesity for theragnostic convenience, focusing on the cytokine and adipokine network in obesity and the significance of the balance of Th1/Th2 immunity. Key Words: Adipokine, Cytokine, Immune homeostasis, Immunological profiling, Obesity INTRODUCTION adipokines, adiponectin and leptin are novel specific hor- mones implicated in the pathogenesis of obesity [4]. The im- Obesity, which involves chronic low-grade inflammation, munological profiling of obesity-related biomarkers will al- has become a global epidemic. This poses a large health bur- low researchers to better understand the complex inter- den, because excess adiposity can lead to an array of chronic actions between classical immunocytes, adipose tissue mac- diseases such as type 2 diabetes, stroke, coronary heart dis- rophages, adipokines and other inflammation-related cyto- ease and high blood pressure [1].
    [Show full text]
  • Interleukin-10, Interleukin- 16 and Interferon-Γ in Serum of Patients with Rheumatoid Arthritis and Correlation with Disease Activity
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Directory of Open Access Journals The Egyptian Journal of Hospital Medicine Vol., 20: 46 – 57 September 2005 I.S.S.N: 12084 1687 –2002 Interleukin-10, Interleukin- 16 and Interferon-γ in serum of patients with rheumatoid arthritis and correlation with disease activity Eman.M.Abdel Rahman, Hamdia.Ezzat, Maha M Abdel Mohsen, Karema Yosef Clinical pathology& Internal Medicine Departments, Faculty of Medicine for girls, Al Azhar University Abstract Rheumatoid arthritis (RA) is a systemic inflammatory disease of unknown etiology. The rheumatoid synovium is characterized by infiltration of T cells, macrophage, B cells, and proliferating fibroblasts which aggressively invade cartilage and bone, thus destroying joints' ability to function. In rheumatoid arthritis (RA) both an imbalance between excessive production of the proinflamatory and ant-inflammatory cytokines and skewing of the T cell to a T helper like response. Cytokines have been shown to play a modulatory role in the pathogenesis of RA. The imunoregulatory cytokine IL-10 increases autoantibody production by B cell stimulates its survival, proliferation and differentiation. Moreover IL-10 inhibits the generation of proinflamatory cytokines and proliferation of T helper lymphocyte. Interleukin 16 might play a role in the pathogenesis of chronic inflammation in RA. It has a proinflammatory properties by promoting recruitment of T cells into the rheumatoid synovium. Also IFN-γ is of interest because of the role it plays in the initiation and perpetuation of T helper cell . Serum level of IL-10, IL-16, and IFN-γ were determined in patients with rheumatoid arthritis in relation to disease activity.
    [Show full text]
  • 24 Biological Modifiers
    Chapter 24 / Biological Modifiers 405 24 Biological Modifiers Alexander Mason, Steven Toms, and Aleck Hercbergs Summary Conventional multimodailty therapies have not altered the dismal prognosis of glioblastoma which has prompted alternative investigational approaches utilising biological modifiers of response.We review here interferon alpha (IFN-D) and beta (IFN-E), interleukin-2 (IL-2), tumor necrosis factor-D TNF, interleukin 4 (IL-4) , monoclonal antibodies to EGFR, EGFRvIII and radio- labeled anti-tenascin monoclonal antibody. A current novel approach is exploitation of some of the biological consequences of thyroid hormone deprivation on tumor biology. In a preliminary Phase I/II trial significant improvement in survival and tumor regression rates in recurrent high grade glioma patients were observed following propylthiouracil induced mild (chemical) hypothyroidism combined with high dose tamoxifen.The background to this approach is reviewed. Key Words: glioblastoma; biological modifiers; hypothyroidism; tamoxifen INTRODUCTION Despite advances in surgical resection, computer assisted radiation therapy, and novel chemotherapeutic agents, survival for malignant glioma remains poor. The 2-yr survival of glioblastoma multiforme (GBM), the most malignant form of glioma, remains less than 20%. In light of poor outcomes with more traditional therapies, a number of alternatives have been explored. Immunotherapy has had some success against tumors such as melanoma and renal cell carcinoma. Cell-based immunotherapy and vaccine trials will be the subject of other chapters. In this chapter we will focus on the role of biological response modifiers in the treatment of malignant glioma Biological response modifiers may be defined as any naturally occurring substance, such as cytokine or hormone, that may be used to influence tumor growth.
    [Show full text]
  • Through an IL-12-Dependent Pathway Tract Inflammation in the Lower
    Bacterial DNA or Oligonucleotides Containing Unmethylated CpG Motifs Can Minimize Lipopolysaccharide-Induced Inflammation in the Lower Respiratory Tract This information is current as Through an IL-12-Dependent Pathway of September 25, 2021. David A. Schwartz, Christine L. Wohlford-Lenane, Timothy J. Quinn and Arthur M. Krieg J Immunol 1999; 163:224-231; ; http://www.jimmunol.org/content/163/1/224 Downloaded from References This article cites 82 articles, 34 of which you can access for free at: http://www.jimmunol.org/content/163/1/224.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1999 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Bacterial DNA or Oligonucleotides Containing Unmethylated CpG Motifs Can Minimize Lipopolysaccharide-Induced Inflammation in the Lower Respiratory Tract Through an IL-12-Dependent Pathway1 David A. Schwartz,2*† Christine L. Wohlford-Lenane,† Timothy J. Quinn,† and Arthur M.
    [Show full text]
  • Review Article Pathogenesis of Chronic Urticaria: an Overview
    Hindawi Publishing Corporation Dermatology Research and Practice Volume 2014, Article ID 674709, 10 pages http://dx.doi.org/10.1155/2014/674709 Review Article Pathogenesis of Chronic Urticaria: An Overview Sanjiv Jain Skin Care Clinic, 108 Darya Ganj, New Delhi 110002, India Correspondence should be addressed to Sanjiv Jain; [email protected] Received 14 April 2014; Accepted 15 June 2014; Published 10 July 2014 Academic Editor: Lajos Kemeny Copyright © 2014 Sanjiv Jain. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria.
    [Show full text]
  • 589.Full-Text.Pdf
    HIV-1 gp120 Induces IL-4 and IL-13 Release from Human Fc εRI+ Cells Through Interaction with the V H3 Region of IgE This information is current as Vincenzo Patella, Giovanni Florio, Angelica Petraroli and of September 26, 2021. Gianni Marone J Immunol 2000; 164:589-595; ; doi: 10.4049/jimmunol.164.2.589 http://www.jimmunol.org/content/164/2/589 Downloaded from References This article cites 62 articles, 32 of which you can access for free at: http://www.jimmunol.org/content/164/2/589.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 26, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2000 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. HIV-1 gp120 Induces IL-4 and IL-13 Release from Human ؉ 1 ⑀ Fc RI Cells Through Interaction with the VH3 Region of IgE Vincenzo Patella, Giovanni Florio, Angelica Petraroli, and Gianni Marone2 HIV-1 glycoprotein (gp) 120 from different clades is a potent stimulus for IL-4 and IL-13 release from basophils purified from healthy individuals seronegative for Abs to HIV-1 and HIV-2.
    [Show full text]