DOCSLIB.ORG

Enhancement by Interleukin 4 of Interleukin 2- Or Antibody-Induced Proliferation of Lymphocytes from Interleukin 2-Treated Cancer Patients1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enhancement by Interleukin 4 of Interleukin 2- Or Antibody-Induced Proliferation of Lymphocytes from Interleukin 2-Treated Cancer Patients1 ICANCER RESEARCH 50. 1160-1 164. Februar} 15. 1990) Enhancement by Interleukin 4 of Interleukin 2- or Antibody-induced Proliferation of Lymphocytes from Interleukin 2-treated Cancer Patients1 Jonathan Treisman, Carl M. Higuchi, John A. Thompson, Steven Gillis, Catherine G. Lindgren, Donald E. Kern, Stanley R. Ridell, Philip D. Greenberg, and Alexander I efer Department of Medicine, Division of Medical Oncolog); University of Washington School of Medicine, Seattle. Has/tinglan 9X195 fJ. T., C. M. H.,J. A. T., C, G. L., D. E. K., S. R. R., P. D. G., A. F.]; and Immunex Corporation, Seattle, H'ashington 98101 [S. G.J ABSTRACT IL-2-activated cells for therapy are usually generated by ob taining PBMC from cancer patients shortly after systemic IL- Systemic interleukin 2 (IL-2) and IL-2-activated lymphocytes have 2 therapy and culturing them with IL-2 in vitro. The cells thus induced tumor regression in some cancer patients. The IL-2-activated cells have usually been generated by obtaining peripheral blood mono- generated for infusion are phenotypically and functionally het nuclear cells (PB1V1C)from cancer patients shortly after systemic IL-2 erogeneous and contain cells with LAK activity (5, 7), as well therapy and culturing them with IL-2 in vitro. In an effort to augment as other cells which may mediate or contribute to antitumor the ex vivogeneration of such cells preactivated in vivo, we examined the responses (8). In an effort to enhance the generation of such proliferative responses of PBIVIC from IL-2-treated cancer patients to cells i/i vitro, several agents which induce a proliferative re several proliferative signals including IL-2, interleukin 4 (II -4). and sponse in normal human PBMC were studied for their possible mitogenic antibodies to CD3 and CD28. Although much is known about proliferative effects on PBMC from IL-2-treated patients. the response of normal PBMC to these signals, the possibility was IL-4 is a multipotent lymphokine which enhances prolifera considered that the response of lymphocytes preactivated by IL-2 in vivo tion of B-cells, T-cells, natural killer cells, and monocytes (9- might differ from that of normal PBMC. Accordingly, PBIVICobtained 17). In normal lymphocytes, IL-4 is comitogenic with antigen from ten normal, healthy controls and from 17 patients with advanced cancer 1 to 3 days after systemic IL-2 therapy were cultured for 4 days (15), lectins (16, 17), and antibodies to CD3 (17). IL-4 can with 11.-4(1000 units/ml) and/or IL-2 (10 units/ml or 1000 units/ml) or augment the generation of antigen-specific cytotoxic T-cells with combinations of 11.-I and ant ¡-('1)3±anti-CD28, and they were (18-20) and can induce non-major histocompatibility complex- then tested for proliferation by ('Hjthymidine incorporation. IL-4 failed restricted LAK activity in human PBMC preactivated with IL- to induce proliferation of normal PBMC and inhibited IL-2-induced 2 (21, 22). In contrast to the pleotropic effects of IL-4, mono proliferation, whereas IL-4 alone induced proliferation in PBMC from clonal antibodies directed against CD3 (anti-CD3) specifically five of 11 IL-2-treated patients and did not inhibit but augmented the activate and induce the proliferation of CD3+ T-cells (23) and proliferation induced by IL-2 (10 units/ml and 1000 units/ml) in PBMC can support the growth of major histocompatibility complex- from six of nine patients and five of 11 patients, respectively. Anti-CD3 restricted T-cells (24) as well as cells with LAK activity (25). induced proliferation in PBMC from eight of nine patients, and the The proliferative response to anti-CD3 can be enhanced using proliferation was consistently augmented by coculture with anti-CD28. Finally, IL-4 significantly augmented the proliferative responses of monoclonal antibodies directed against CD28, a M, 44,000 PBMC from IL-2-treated patients to anti-CD3, as well as to the combi homodimer found on approximately 80% of peripheral T-cells nation of anti-CD3 and anti-CD28. Thus, in PBMC from IL-2-treated (26). The proliferative response of normal lymphocytes to anti- cancer patients, IL-4 enhanced the in vitro proliferation induced by IL-2 CD3 is also known to be enhanced by IL-4. or by anti-CD3 ±anti-CD28. The results suggest that IL-4 and/or Although much is known about the proliferative response of mitogenic antibodies may be useful in augmenting the ex vivo generation normal lymphocytes to these agents, the response of lympho of lymphocytes for clinical adoptive ¡mmunotherapy. cytes from IL-2-treated patients, i.e., cells which have been preactivated in vivo by IL-2, and, potentially, by other inter INTRODUCTION mediary lymphokines and cytokines, may be different from that of normal lymphocytes. For example, IL-4 inhibits IL-2-in- The systemic administration of IL-2'1 and autologous lym duced LAK activity in normal human PBMC, but enhances IL- phocytes activated by culture with IL-2 has induced tumor 2-induced LAK activity in PBMC preactivated by IL-2 (21, 22). regression in some cancer patients (1-3). However, the re Accordingly, the proliferative effects of IL-4 and mitogenic sponses have been observed in only a minority of patients, and antibodies on PBMC from IL-2-treated cancer patients were the doses of IL-2 required have usually been toxic (4, 5). In examined. The data demonstrate that (a) in contrast to the animal models, the antitumor effects observed correlated with inhibition of IL-2-induced proliferation by IL-4 in normal the amount of IL-2 administered and with the number of PBMC, IL-4 alone induced substantial proliferation and aug activated cells infused (6). Thus, the development of techniques mented the proliferative response to IL-2 in PBMC from the to augment the generation of activated lymphocytes ex vivo majority of the patients tested; (¿>)anti-CD3induced prolifera may potentially enhance tumor responses in vivo. One approach tion of patient PBMC; (c) anti-CD28 enhanced the proliferative to this goal is the use of other proliferative signals in addition response to anti-CD3; and (d) IL-4 augmented the proliferative to or in lieu of IL-2. response to both mitogenic antibodies. The results suggest that Received 10/10/89: accepted 11/13/89. IL-4 ±mitogenic antibodies may have a role in the ex vivo The costs of publication of this article were defrayed in part by the payment generation of lymphocytes for adoptive immunotherapy trials. of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. ' This work was supported in part by Grant CA 09515 and Contract NO1- CM47668 awarded by the National Cancer Institute. Department of Health and MATERIALS AND METHODS Human Services. Some of the data in this manuscript were presented at the 80th Annual Meeting of the American Association for Cancer Research. May 1989. Study Population and Blood Sampling. Seventeen patients aged 30 to ' To whom requests for reprints should be addressed, at the Department of 71 yr with metastatic renal cell carcinoma (9 patients), melanoma (6 Medicine. Division of Oncology, RM-17, University of Washington, Seattle. WA patients), diffuse histiocytic lymphoma (one patient), and carcinoma of 98195. JThe abbreviations used are: IL-2, interleukin 2; IL-4, interleukin 4; LAK, the colon (one patient) participated in a Phase I/II trial of IL-2 and lymphokine-activated killer; PBMC, peripheral blood mononuclear cells; dThd, adoptive transfer of LAK cells (3, 4). Patients had no preceding treat thymidine; p55, M, 55,000 protein; TIL, tumor-infiltrating lymphocytes. ments within 4 wk of study and had Karnofsky scores >70% at initiation 1160 Downloaded from cancerres.aacrjournals.org on September 27, 2021. © 1990 American Association for Cancer Research. IL-4 ENHANCEMENT OF PROLIFERATION AFTER IL-2 THERAPY of IL-2 therapy. All patients received systemic recombinant human of IL-2, which is normally used for LAK cell generation in IL-2 (Hoffman-LaRoche Inc., Nutley, NJ), with treatment cycles con clinical trials (1-3), was also studied. The results are shown in sisting of IL-2 administered by continuous i.v. infusion for 5 consecutive Table 1. IL-4 alone failed to induce proliferation and inhibited days. Seven patients received 1 to 4 treatment cycles of IL-2 (3 x IO6 IL-2-driven proliferation in PBMC from healthy controls (n = units/m2/day) (4, 5), and 10 patients received a single cycle of IL-2 at a higher dose (6 x IO6units/m2/day) (3). Blood samples were collected 7), as previously reported (16, 22, 31). By contrast, IL-4 induced proliferation in PBMC from 5 of 11 IL-2-treated patients. 1 to 3 days after termination of a treatment cycle, which corresponded Furthermore, rather than inhibit proliferation induced by IL-2, to the time of initial leukapheresis for ex vivo cell culture for LAK generation. Blood was collected from healthy controls on the day of IL-4 augmented proliferation induced by IL-2 (10 units/ml or assay. 1000 units/ml) in PBMC from 6 of 9 and 5 of 11 IL-2-treated Preparation of Human Blood Mononuclear Cells and T-Cells. PBMC patients, respectively. were isolated from heparinized peripheral blood by Ficoll-Hypaque Dependence of the Proliferative Effects of IL-4 upon Preacti density gradient separation. For purification of T-cells, PBMC were vation of Lymphocytes by IL-2 in Vivo or in Vitro. To determine adherence depleted of macrophages followed by resetting with 2-amino- whether the ability of IL-4 to augment IL-2-induced prolifera ethyl-isothiouronium bromide-treated sheep RBC (27).
Load more

Recommended publications
  • Levels of Interleukin-2, Interferon- , and Interleukin-4 In
    Levels of Interleukin-2, Interferon-␥, and Interleukin-4 in Bronchoalveolar Lavage Fluid From Patients With Mycoplasma Pneumonia: Implication of Tendency Toward Increased Immunoglobulin E Production Young Yull Koh, MD*; Yang Park, MD*; Hoan Jong Lee, MD*; and Chang Keun Kim, MD‡ ABSTRACT. Objective. In connection with the possi- ABBREVIATIONS. IgE, immunoglobulin E; TH1, T helper type 1; ble relationship between Mycoplasma infection and the TH2, T helper type 2; IFN, interferon; IL, interleukin; BAL, bron- onset of asthma, several studies have shown not only a choalveolar lavage; FB, fiber-optic bronchoscopy; SD, standard high level of serum total immunoglobulin E (IgE) but deviation. also the production of IgE specific to Mycoplasma or common allergens during the course of Mycoplasma in- fection. It has been suggested that the balance of T helper esults of several studies over the past decade type 1 (TH1)/T helper type 2 (TH2) immune response have provided evidence linking Mycoplasma may regulate the synthesis of IgE. The objective of this Rinfection with asthma exacerbation and have study was to investigate the pattern of cytokine response raised the possibility that Mycoplasma infection is a (TH1 or TH2) during an episode of acute lower respira- factor in the pathogenesis of asthma. An acute exac- tory tract infection caused by Mycoplasma pneumoniae. erbation of wheezing in asthmatic participants in Study Design. Using a bronchoalveolar lavage (BAL) association with Mycoplasma infection has been well- with flexible bronchoscopy procedure, this study deter- 1,2 mined the levels of interleukin (IL)-2, interferon (IFN)-␥ documented. In addition, Mycoplasma pneumoniae (TH1), and IL-4 (TH2) in the supernatant of BAL fluid as has been found in the lower airways of chronic, well as the BAL cellular profiles of patients with Myco- stable asthmatics with a greater frequency than in -These results were com- control participants,3 suggesting a pathogenic mech .(14 ؍ plasma pneumonia (n pared with those of patients with pneumococcal pneu- anism in chronic asthma.
    [Show full text]
  • Modulation of the Inflammatory Response After Spinal Cord Injury
    ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en MODULATION OF THE INFLAMMATORY RESPONSE AFTER SPINAL CORD INJURY Presented by Jesús Amo Aparicio ACADEMIC DISSERTATION To obtain the degree of PhD in Neuroscience by the Universitat Autònoma de Barcelona 2019 Directed by Dr. Rubèn López Vales Tutorized by Dr. Xavier Navarro Acebes INDEX SUMMARY Page 7 INTRODUCTION Page 13 - Spinal cord Page 15 - Spinal cord injury Page 17 - Incidence and causes Page 18 - Types of SCI Page 18 - Biological events after SCI Page 20 - Studying SCI Page 24 - Animal models Page 24 - Lesion models Page 24 - Current therapies for SCI Page 25 - Basic principles of the immune system Page 27 - Innate immune response Page 27 - Adaptive immune response Page 28 - Inflammatory response Page 29 - Inflammatory response after SCI Page 30 - Modulation of injury environment Page 36 - Interleukin 1 Page 36 - Interleukin 37 Page 40 - Interleukin 13 Page 44 OBJECTIVES Page 47 MATERIALS AND METHODS Page 51
    [Show full text]
  • IL-1Β Induces the Rapid Secretion of the Antimicrobial Protein IL-26 From
    Published June 24, 2019, doi:10.4049/jimmunol.1900318 The Journal of Immunology IL-1b Induces the Rapid Secretion of the Antimicrobial Protein IL-26 from Th17 Cells David I. Weiss,*,† Feiyang Ma,†,‡ Alexander A. Merleev,x Emanual Maverakis,x Michel Gilliet,{ Samuel J. Balin,* Bryan D. Bryson,‖ Maria Teresa Ochoa,# Matteo Pellegrini,*,‡ Barry R. Bloom,** and Robert L. Modlin*,†† Th17 cells play a critical role in the adaptive immune response against extracellular bacteria, and the possible mechanisms by which they can protect against infection are of particular interest. In this study, we describe, to our knowledge, a novel IL-1b dependent pathway for secretion of the antimicrobial peptide IL-26 from human Th17 cells that is independent of and more rapid than classical TCR activation. We find that IL-26 is secreted 3 hours after treating PBMCs with Mycobacterium leprae as compared with 48 hours for IFN-g and IL-17A. IL-1b was required for microbial ligand induction of IL-26 and was sufficient to stimulate IL-26 release from Th17 cells. Only IL-1RI+ Th17 cells responded to IL-1b, inducing an NF-kB–regulated transcriptome. Finally, supernatants from IL-1b–treated memory T cells killed Escherichia coli in an IL-26–dependent manner. These results identify a mechanism by which human IL-1RI+ “antimicrobial Th17 cells” can be rapidly activated by IL-1b as part of the innate immune response to produce IL-26 to kill extracellular bacteria. The Journal of Immunology, 2019, 203: 000–000. cells are crucial for effective host defense against a wide and neutrophils.
    [Show full text]
  • The Cross-Talk Between Neurons and Microglia Through Interleukin-4 After Ischemic Injury
    The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 8-2018 The Cross-Talk Between Neurons and Microglia Through Interleukin-4 After Ischemic Injury Shun-Ming Ting Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Medicine and Health Sciences Commons Recommended Citation Ting, Shun-Ming, "The Cross-Talk Between Neurons and Microglia Through Interleukin-4 After Ischemic Injury" (2018). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 892. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/892 This Thesis (MS) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. THE CROSS-TALK BETWEEN NEURONS AND MICROGLIA THROUGH INTERLEUKIN-4 AFTER ISCHEMIC INJURY by Shun-Ming Ting, M.S. APPROVED: ______________________________ Jaroslaw Aronowski, Ph.D. Advisory
    [Show full text]
  • Evolutionary Divergence and Functions of the Human Interleukin (IL) Gene Family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W
    UPDATE ON GENE COMPLETIONS AND ANNOTATIONS Evolutionary divergence and functions of the human interleukin (IL) gene family Chad Brocker,1 David Thompson,2 Akiko Matsumoto,1 Daniel W. Nebert3* and Vasilis Vasiliou1 1Molecular Toxicology and Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO 80045, USA 2Department of Clinical Pharmacy, University of Colorado Denver, Aurora, CO 80045, USA 3Department of Environmental Health and Center for Environmental Genetics (CEG), University of Cincinnati Medical Center, Cincinnati, OH 45267–0056, USA *Correspondence to: Tel: þ1 513 821 4664; Fax: þ1 513 558 0925; E-mail: [email protected]; [email protected] Date received (in revised form): 22nd September 2010 Abstract Cytokines play a very important role in nearly all aspects of inflammation and immunity. The term ‘interleukin’ (IL) has been used to describe a group of cytokines with complex immunomodulatory functions — including cell proliferation, maturation, migration and adhesion. These cytokines also play an important role in immune cell differentiation and activation. Determining the exact function of a particular cytokine is complicated by the influence of the producing cell type, the responding cell type and the phase of the immune response. ILs can also have pro- and anti-inflammatory effects, further complicating their characterisation. These molecules are under constant pressure to evolve due to continual competition between the host’s immune system and infecting organisms; as such, ILs have undergone significant evolution. This has resulted in little amino acid conservation between orthologous proteins, which further complicates the gene family organisation. Within the literature there are a number of overlapping nomenclature and classification systems derived from biological function, receptor-binding properties and originating cell type.
    [Show full text]
  • Expression of Interleukin-4 but Not of Interleukin-10 from a Replicative Herpes Simplex Virus Type 1 Viral Vector Precludes Experimental Allergic Encephalomyelitis
    Gene Therapy (2001) 8, 769–777 2001 Nature Publishing Group All rights reserved 0969-7128/01 $15.00 www.nature.com/gt RESEARCH ARTICLE Expression of interleukin-4 but not of interleukin-10 from a replicative herpes simplex virus type 1 viral vector precludes experimental allergic encephalomyelitis E Broberg1,2,3, N Seta¨la¨ 1,3,MRo¨ytta¨4, A Salmi1, J-P Era¨linna1,5,BHe6, B Roizman6 and V Hukkanen1,2 Departments of 1Virology, 4Pathology, 5Neurology and 2MediCity Research Laboratory, University of Turku, Turku; 3Turku Graduate School of Biomedical Sciences, Turku, Finland; and 6The Marjorie B Kovler Viral Oncology Laboratories, University of Chicago, Chicago, IL, USA We have used interleukin (IL)-4 and -10-producing HSV-1 any infection, mice infected with backbone virus R3659 and ␥ 134.5 deletion viruses in gene therapy of a BALB/c model mock-infected mice. Weights and symptoms of the mice of experimental allergic encephalomyelitis (EAE), a T cell- were recorded daily and the tissue specimens were col- mediated demyelinating disease of the central nervous sys- lected at specific time-points. The results indicate that the tem. It is known that in EAE of mice the Th2-type cytokines intracranial infection with IL-4-producing virus (1) precludes are down-regulated and the Th1-type cytokines up-regulated EAE symptoms, (2) protects the spinal cord from massive during the onset and relapse of the disease. Therefore, we leukocyte infiltrations and (3) prevents demyelination and tested two HSV-1 recombinants expressing the Th2-type axonal loss. The IL-10-expressing virus R8308 did not have cytokines IL-4 and IL-10.
    [Show full text]
  • IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells
    cells Article IL-21 in Conjunction with Anti-CD40 and IL-4 Constitutes a Potent Polyclonal B Cell Stimulator for Monitoring Antigen-Specific Memory B Cells Fridolin Franke 1,2, Greg A. Kirchenbaum 1 , Stefanie Kuerten 2 and Paul V. Lehmann 1,* 1 Research & Development Department, Cellular Technology Limited, Shaker Heights, OH 44122, USA; [email protected] (F.F.); [email protected] (G.A.K.) 2 Institute of Anatomy and Cell Biology, Friedrich-Alexander University Erlangen-Nürnberg, 91054 Erlangen, Germany; [email protected] * Correspondence: [email protected]; Tel.: +1-216-965-6311 Received: 3 December 2019; Accepted: 12 February 2020; Published: 13 February 2020 Abstract: Detection of antigen-specific memory B cells for immune monitoring requires their activation, and is commonly accomplished through stimulation with the TLR7/8 agonist R848 and IL-2. To this end, we evaluated whether addition of IL-21 would further enhance this TLR-driven stimulation approach; which it did not. More importantly, as most antigen-specific B cell responses are T cell-driven, we sought to devise a polyclonal B cell stimulation protocol that closely mimics T cell help. Herein, we report that the combination of agonistic anti-CD40, IL-4 and IL-21 affords polyclonal B cell stimulation that was comparable to R848 and IL-2 for detection of influenza-specific memory B cells. An additional advantage of anti-CD40, IL-4 and IL-21 stimulation is the selective activation of IgM+ memory B cells, as well as the elicitation of IgE+ ASC, which the former fails to do. Thereby, we introduce a protocol that mimics physiological B cell activation through helper T cells, including induction of all Ig classes, for immune monitoring of antigen-specific B cell memory.
    [Show full text]
  • IL-4 Abrogates TH17 Cell-Mediated Inflammation by Selective Silencing of IL-23 in Antigen-Presenting Cells
    IL-4 abrogates TH17 cell-mediated inflammation by selective silencing of IL-23 in antigen-presenting cells Emmanuella Guenovaa,b,c,1,2, Yuliya Skabytskaa,1, Wolfram Hoetzeneckera,b,c,1, Günther Weindla,d, Karin Sauera, Manuela Thama, Kyu-Won Kime, Ji-Hyeon Parke, Ji Hae Seoe,f, Desislava Ignatovac, Antonio Cozzioc, Mitchell P. Levesquec, Thomas Volza,g, Martin Köberlea,g, Susanne Kaeslera, Peter Thomash, Reinhard Mailhammeri,3, Kamran Ghoreschia, Knut Schäkelj, Boyko Amarovk, Martin Eichnerl, Martin Schallera, Rachael A. Clarkb, Martin Röckena,2, and Tilo Biedermanna,g,2 aDepartment of Dermatology, Eberhard Karls University, 72076 Tübingen, Germany; dInstitute of Pharmacy, Department of Pharmacology and Toxicology, Freie Universität, 14195 Berlin, Germany; eNeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea; fDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742, Republic of Korea; cDepartment of Dermatology, University Hospital of Zürich, 8091 Zürich, Switzerland; hDepartment of Dermatology and Allergology, Ludwig Maximilians University, 80337 Munich, Germany; iInstitute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 81377 Munich, Germany; jDepartment of Dermatology, Heidelberg University Hospital, 69115 Heidelberg, Germany; kInstitute
    [Show full text]
  • Suppresses Interleukin 1 Production but Up-Regulates Gene Expression and Synthesis of Interleukin 1 Receptor Antagonist EDOUARD VANNIER, LAURIE C
    Proc. Nail. Acad. Sci. USA Vol. 89, pp. 4076-4080, May 1992 Medical Sciences Coordinated antiinflammatory effects of interleukin 4: Interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist EDOUARD VANNIER, LAURIE C. MILLER, AND CHARLES A. DINARELLO* Departments of Medicine and Pediatrics, Tufts University School of Medicine and New England Medical Center, Boston, MA 02111 Communicated by Anthony Cerami, January 23, 1992 (received for review December 4, 1991) ABSTRACT Interleukin 1 receptor antagonist (IL-lra), a occupancy of its receptor (16, 17). This IL-1 inhibitor has naturally occurring polypeptide with amino acid sequence been recently cloned, expressed, and characterized (18-20). homology to interleukin la (IL-la) and interleukin 113 (IL-1.8), Because it binds to both IL-1 receptors (18, 21) without prevents Escherichia coli-induced shock and death. Both IL-i agonist activity (22), and inhibits IL-1 binding and biological and IL-lra are produced by monocytes stimulated with lipo- activities (18, 23, 24), the IL-1 inhibitor has been renamed the polysaccharide (LPS). Because interleukin 4 (IL-4) suppresses IL-1 receptor antagonist (IL-lra). Human IL-lra has 19% IL-1 production, we investigated whether IL-4 modulated amino acid homology to human IL-la and 26% homology to IL-ira synthesis in LPS-stimulated human peripheral blood human IL-ip (19) and is thought to be a member of the IL-1 mononuclear cells. IL-113 and IL-lra were measured by specific gene family (25). IL-4 suppresses IL-1 and other monocyte- RIAs.
    [Show full text]
  • Associations of Interleukin-1 (IL-1)
    Kari Luotola ASSOCIATIONS OF INTERLEUKIN-1 (IL-1) GENE VARIATION AND IL-1 RECEPTOR ANTAGONIST PHENOTYPES WITH IMMUNOLOGICAL RESPONSES, METABOLIC DYSREGULATION AND TYPE 2 DIABETES ACADEMIC DISSERTATION To be presented, with the permission of the Medical Faculty, University of Helsinki, for public examination in Auditorium 2 at Biomedicum on May 28th 2011, at 12 noon Department of Medicine, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland Helsinki 2011 Copyright © 2011 Kari Luotola Original publications reprinted with permission ISBN 978-952-92-9017-8 (paperback) ISBN 978-952-10-6966-6 (PDF) http://helda.helsinki.fi Yliopistopaino Helsinki, Finland 2011 2 Supervised by Professor Veikko Salomaa, MD, PhD National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki, Finland Reviewed by Professor Jorma Viikari, MD, PhD Department of Internal Medicine, Turku University Hospital, Turku, Finland Professor Markku Savolainen, MD, PhD Department of Internal Medicine, University of Oulu and Oulu University Hospital, Oulu, Finland Opponent Professor Olli Raitakari, MD, PhD Department of Clinical Physiology, Turku University Central Hospital and University of Turku, Turku, Finland 3 … The wind it was so insistent With tales of a stormy south … I walked out this morning It was like a veil had been removed from before my eyes For the first time I saw the work of heaven … And inside every turning leaf Is the pattern of an older tree The shape of our future The shape of all our history And
    [Show full text]
  • Regulation of IL-17A Responses in Human Airway Smooth Muscle Cells
    Kwofie et al. Respiratory Research (2015) 16:14 DOI 10.1186/s12931-014-0164-4 RESEARCH Open Access Regulation of IL-17A responses in human airway smooth muscle cells by Oncostatin M Karen Kwofie1, Matthew Scottˆ, Rebecca Rodrigues1, Jessica Guerette1, Katherine Radford2, Parameswaran Nair2 and Carl D Richards1,3* Abstract Background: Regulation of human airway smooth muscle cells (HASMC) by cytokines contributes to chemotactic factor levels and thus to inflammatory cell accumulation in lung diseases. Cytokines such as the gp130 family member Oncostatin M (OSM) can act synergistically with Th2 cytokines (IL-4 and IL-13) to modulate lung cells, however whether IL-17A responses by HASMC can be altered is not known. Objective: To determine the effects of recombinant OSM, or other gp130 cytokines (LIF, IL-31, and IL-6) in regulating HASMC responses to IL-17A, assessing MCP-1/CCL2 and IL-6 expression and cell signaling pathways. Methods: Cell responses of primary HASMC cultures were measured by the assessment of protein levels in supernatants (ELISA) and mRNA levels (qRT-PCR) in cell extracts. Activation of STAT, MAPK (p38) and Akt pathways were measured by immunoblot. Pharmacological agents were used to assess the effects of inhibition of these pathways. Results: OSM but not LIF, IL-31 or IL-6 could induce detectable responses in HASMC, elevating MCP-1/CCL2, IL-6 levels and activation of STAT-1, 3, 5, p38 and Akt cell signaling pathways. OSM induced synergistic action with IL-17A enhancing MCP-1/CCL-2 and IL-6 mRNA and protein expression, but not eotaxin-1 expression, while OSM in combination with IL-4 or IL-13 synergistically induced eotaxin-1 and MCP-1/CCL2.
    [Show full text]
  • IL-4 During Th17 Maturation Sensitivity and Resistance to Regulation By
    Sensitivity and Resistance to Regulation by IL-4 during Th17 Maturation Laura A. Cooney, Keara Towery, Judith Endres and David A. Fox This information is current as of September 30, 2021. J Immunol 2011; 187:4440-4450; Prepublished online 26 September 2011; doi: 10.4049/jimmunol.1002860 http://www.jimmunol.org/content/187/9/4440 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2011/09/27/jimmunol.100286 Material 0.DC1 References This article cites 45 articles, 20 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/187/9/4440.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 30, 2021 • 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: 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 © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Sensitivity and Resistance to Regulation by IL-4 during Th17 Maturation Laura A. Cooney,1 Keara Towery,2 Judith Endres, and David A.
    [Show full text]