Published 6 issues per year
ISSN Print: 1040-8401
ISSN Online: 2162-6472
Indexed in
lnterleukin-1 Receptor Antagonist
ABSTRACT
The interleukin-1 receptor antagonist (IL-lra) is unusual in that it is the only known naturally occurring, cytokine receptor antagonist with no apparent agonist function. Over the last 5 years, since the cloning of the IL-lra cDNA sequence, there has been intensive research on the genetics, regulation, and potential therapeutic value of this protein. The later discovery of a second form of IL-lra in 1991 has complicated the picture. Whereas the originally described IL-lra is predominantly glycosylated and secreted (sIL-lra), the alternative isoform is unglycosylated and intracellular (icIL-lra). Although the biological roles of the two forms are still open to question, IL-lra is likely to be of great importance in the pathogenesis of both acute and chronic inflammatory diseases. A large body of evidence for this conclusion has come from animal models of inflammatory disease that respond well to administration of exogenous IL-lra. A role for recombinant IL-lra in the management of human disease is still under investigation. The two forms of IL-lra are encoded by a single gene by alternative usage of two first exons. Expression of sIL-lra and icIl-lra is regulated by two promoters. In this review I explore the genetics of the gene encoding IL-lra (IL-1RN) and the mechanisms of IL-lra gene activation to produce sIL-lra and icIL-lra. Also, possible biological roles for these immunomodulators in health and disease are discussed.
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Schwabe M., Hartert A.-M., Bertz H., Finke J., Treatment with granulocyte colony-stimulating factor increases interleukin-1 receptor antagonist levels during engraftment following allogeneic stem-cell transplantation, European Journal of Clinical Investigation, 34, 11, 2004. Crossref
-
Lin Kai-Wei, Chen Shu-Ching, Chang Fu-Hsiung, Kung John T., Hsu Brend Ray-Sea, Lin Rong-Hwa, The roles of interleukin-1 and interleukin-1 receptor antagonist in antigen-specific immune responses, Journal of Biomedical Science, 9, 1, 2002. Crossref
-
Campos Maria I. G., Santos Maria C. L. G., Trevilatto Paula C., Scarel-Caminaga Raquel M., Bezerra Fabio J. B., Line Sergio R. P., Evaluation of the relationship between interleukin-1 gene cluster polymorphisms and early implant failure in non-smoking patients, Clinical Oral Implants Research, 16, 2, 2005. Crossref
-
Moldoveanu Andrei I., Shephard Roy J., Shek Pang N., The Cytokine Response to Physical Activity and Training, Sports Medicine, 31, 2, 2001. Crossref
-
Vamvakopoulos Joannis E., Taylor Craig J., Green Colin, McNeil Keith, Wallwork John, Goodman Reyna, Metcalfe Su M., Interleukin 1 and Chronic Rejection: Possible Genetic Links in Human Heart Allografts, American Journal of Transplantation, 2, 1, 2002. Crossref
-
Mehler Mark F., Kessler John A., Cytokines in Brain Development and Function, in Cytokines, 52, 1998. Crossref
-
Borsody Mark K., Weiss Jay M., Peripheral endotoxin causes long-lasting changes in locus coeruleus activity via IL-1 in the brain, Acta Neuropsychiatrica, 14, 6, 2002. Crossref
-
Ohtsuki Toshiho, Ruetzler Christi A., Tasaki Kaoru, Hallenbeck John M., Interleukin-1 Mediates Induction of Tolerance to Global Ischemia in Gerbil Hippocampal CA1 Neurons, Journal of Cerebral Blood Flow & Metabolism, 16, 6, 1996. Crossref
-
Boudjellab N, Chan-Tang H.S, Zhao X, Bovine interleukin-1 expression by cultured mammary epithelial cells (MAC-T) and its involvement in the release of MAC-T derived interleukin-8, Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 127, 2, 2000. Crossref
-
Lundqvist Elisabet Nylander, Egelrud Torbjörn, Biologically active, alternatively processed interleukin-1β in psoriatic scales, European Journal of Immunology, 27, 9, 1997. Crossref
-
Rezk Noha A., Mohamad Hanan S., Influence of Interleukin-1 Gene Cluster Polymorphisms on the Susceptibility and Outcomes of Acute Stroke in Egyptian Patients, Cell Biochemistry and Biophysics, 71, 2, 2015. Crossref
-
El-Shabrawi Y., Ardjomand N., Nachweis von Interleukin-1 und Interleukin-1 Rezeptorantagonist in intraokulären Flüssigkeiten von Uveitispatienten, Spektrum der Augenheilkunde, 13, 4, 1999. Crossref
-
Sapey Elizabeth, Ahmad Ali, Bayley Darren, Newbold Paul, Snell Noel, Rugman Paul, Stockley Robert A., Imbalances Between Interleukin-1 and Tumor Necrosis Factor Agonists and Antagonists in Stable COPD, Journal of Clinical Immunology, 29, 4, 2009. Crossref
-
Zou Jun, Cunningham Charles, Secombes Christopher J., The rainbow trout Oncorhynchus mykiss interleukin-1β gene has a different organization to mammals and undergoes incomplete splicing, European Journal of Biochemistry, 259, 3, 2001. Crossref
-
Montes Claudia Cristina, Alvim-Pereira Fabiano, de Castilhos Bruno Borges, Sakurai Marcos Luciano Lopes, Olandoski Marcia, Trevilatto Paula Cristina, Analysis of the association ofIL1B(C+3954T) andIL1RN(intron 2) polymorphisms with dental implant loss in a Brazilian population, Clinical Oral Implants Research, 20, 2, 2009. Crossref
-
Howren M Bryant, Lamkin Donald M., Suls Jerry, Associations of Depression With C-Reactive Protein, IL-1, and IL-6: A Meta-Analysis, Psychosomatic Medicine, 71, 2, 2009. Crossref
-
Atrasheuskaya Alena, Petzelbauer Peter, Fredeking Terry M, Ignatyev George, Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection, FEMS Immunology & Medical Microbiology, 35, 1, 2003. Crossref
-
Humphreys Neil E., Grencis Richard K., IL-1-dependent, IL-1R1-independent resistance to gastrointestinal nematodes, European Journal of Immunology, 39, 4, 2009. Crossref
-
Yu P.W, Schuler L.A, Rejman J.J, Chen H.T, Gosink K, Kehrli M, Mattocks L, Nonnecke B, Czuprynski C.J, Regulation of bovine interleukin-1 receptors, Veterinary Immunology and Immunopathology, 63, 1-2, 1998. Crossref
-
Kupper Thomas S., The Utility of Transgenic Mouse Models in the Study of Cutaneous Immunology and Inflammation, The Journal of Dermatology, 23, 11, 1996. Crossref
-
Samson Lindy M., Allen Upton D., Creery W.David, Diaz-Mitoma Francisco, Singh Ram N., Elevated interleukin-1 receptor antagonist levels in pediatric sepsis syndrome, The Journal of Pediatrics, 131, 4, 1997. Crossref
-
Chizzolini Carlo, Dayer Jean-Michel, Cytokine Inhibitors, in Encyclopedia of Immunology, 1998. Crossref
-
Ignatyev George, Steinkasserer Alexander, Streltsova Marina, Atrasheuskaya Alena, Agafonov Alexander, Lubitz Werner, Experimental study on the possibility of treatment of some hemorrhagic fevers, Journal of Biotechnology, 83, 1-2, 2000. Crossref
-
Zou Jun, Grabowski Peter S, Cunningham Charles, Secombes Christopher J, MOLECULAR CLONING OF INTERLEUKIN 1β FROM RAINBOW TROUT ONCORHYNCHUS MYKISS REVEALS NO EVIDENCE OF AN ICE CUT SITE, Cytokine, 11, 8, 1999. Crossref
-
Hailes Walter S., Slivka Dustin, Cuddy John, Ruby Brent C., Human plasma inflammatory response during 5 days of exercise training in the heat, Journal of Thermal Biology, 36, 5, 2011. Crossref
-
Bernhofer L.P, Barkovic S, Appa Y, Martin K.M, IL-1α and IL-1ra secretion from epidermal equivalents and the prediction of the irritation potential of mild soap and surfactant-based consumer products, Toxicology in Vitro, 13, 2, 1999. Crossref
-
Yamshchikov Vladimir F, Mishina Margarita, Cominelli Fabio, A POSSIBLE ROLE OF IL-1RA 3′-UNTRANSLATED REGION IN MODULATION OF PROTEIN PRODUCTION, Cytokine, 17, 2, 2002. Crossref
-
Walker Josef, Rigley Kevin, Gene expression profiling in human peripheral blood mononuclear cells using high-density filter-based cDNA microarrays, Journal of Immunological Methods, 239, 1-2, 2000. Crossref
-
Mittal Rama D., Bid Hemant K., Manchanda Parmeet K., Genotype and haplotype determination of IL1B (g. −511C>T and g. +3954C>T) and (IL1RN) in pediatric nephrolithiasis, Clinica Chimica Acta, 379, 1-2, 2007. Crossref
-
Stienstra Rinke, Mandard Stéphane, Tan Nguan Soon, Wahli Walter, Trautwein Christian, Richardson Terrilyn A., Lichtenauer-Kaligis Elgin, Kersten Sander, Müller Michael, The Interleukin-1 receptor antagonist is a direct target gene of PPARα in liver, Journal of Hepatology, 46, 5, 2007. Crossref
-
Holtkamp G.M, Kijlstra A, Peek R, de Vos A.F, Retinal Pigment Epithelium-immune System Interactions: Cytokine Production and Cytokine-induced Changes, Progress in Retinal and Eye Research, 20, 1, 2001. Crossref
-
Pita Ignacio, Jelaso Anna M., Ide Charles F., IL‐1 β increases intracellular calcium through an IL‐1 type 1 receptor mediated mechanism in C6 astrocytic cells , International Journal of Developmental Neuroscience, 17, 8, 1999. Crossref
-
Ping-Ke Fang, Xu-Chen Ma, Da-Long Ma, Kai-Yuan Fu, Determination of interleukin-1 receptor antagonist, interleukin-10, and transforming growth factor-β1 in synovial fluid aspirates of patients with temporomandibular disorders, Journal of Oral and Maxillofacial Surgery, 57, 8, 1999. Crossref
-
Komeda Mototane, Roessler Blake J., Raphael Yehoash, The influence of interleukin-1 receptor antagonist transgene on spiral ganglion neurons, Hearing Research, 131, 1-2, 1999. Crossref
-
Siemion I.Z., Kluczyk A., Wieczorek Zbigniew, Anti-IL-1 Activity of Peptide Fragments of IL-1 Family Proteins, Peptides, 19, 2, 1998. Crossref
-
Weigand Markus A, Hörner Christian, Bardenheuer Hubert J, Bouchon Axel, The systemic inflammatory response syndrome, Best Practice & Research Clinical Anaesthesiology, 18, 3, 2004. Crossref
-
Bernhofer L.P, Seiberg M, Martin K.M, The Influence of the Response of Skin Equivalent Systems to Topically Applied Consumer Products by Epithelial--Mesenchymal Interactions, Toxicology in Vitro, 13, 2, 1999. Crossref
-
Mittal Rama D., Bid Hemant K., Ghoshal Uday C., IL-1 receptor antagonist (IL-1Ra) gene polymorphism in patients with inflammatory bowel disease in India, Scandinavian Journal of Gastroenterology, 40, 7, 2005. Crossref
-
Hurme Mikko, Lahdenpohja Nina, Santtila Sari, Gene polymorphisms of interleukins 1 and 10 in infectious and autoimmune diseases, Annals of Medicine, 30, 5, 1998. Crossref
-
Ashraf Saeed, Bhattacharya Kausik, Tian Yi, Watterson Kevin, Cytokine and S100B levels in paediatric patients undergoing corrective cardiac surgery with or without total circulatory arrest, European Journal of Cardio-Thoracic Surgery, 16, 1, 1999. Crossref
-
Gabriel A. S., Ahnve S., Wretlind B., Martinsson A., IL-6 and IL-1 receptor antagonist in stable angina pectoris and relation of IL-6 to clinical findings in acute myocardial infarction, Journal of Internal Medicine, 248, 1, 2000. Crossref
-
Cook Matthew C, Immunology of trauma, Trauma, 3, 2, 2001. Crossref
-
Wenneras Christine, Ave Patrick, Huerre Michel, Arondel Josette, Ulevitch Richard, Mathison John, Sansonetti Philippe, Blockade of CD14 aggravates experimental shigellosis, Journal of Endotoxin Research, 7, 6, 2001. Crossref
-
Lin Juway, Chang Ya-Jen, Yang Wen-Bin, Yu Alice L., Wong Chi-Huey, Spencer Juliet, The Multifaceted Effects of Polysaccharides Isolated from Dendrobium huoshanense on Immune Functions with the Induction of Interleukin-1 Receptor Antagonist (IL-1ra) in Monocytes, PLoS ONE, 9, 4, 2014. Crossref
-
Kallianpur Asha R, Bradford Yuki, Mody Rajal K, Garman Katie N, Comstock Nicole, Lathrop Sarah L, Lyons Carol, Saupe Amy, Wymore Katie, Canter Jeffrey A, Olson Lana M, Palmer Amanda, Jones Timothy F, Genetic Susceptibility to Postdiarrheal Hemolytic-Uremic Syndrome After Shiga Toxin–Producing Escherichia coli Infection: A Centers for Disease Control and Prevention FoodNet Study, The Journal of Infectious Diseases, 217, 6, 2018. Crossref
-
Moser C., Ilg A., Wehling P., Zytokinantagonisten in der Behandlung der Gonarthrose, in Knie, 2007. Crossref
-
Vogel Hans Gerhard, Analgesic, Anti-inflammatory, and Anti-pyretic Activity, in Drug Discovery and Evaluation, 2007. Crossref
-
Blix I. J. Schytte, Helgeland K., Hvattum E., Lyberg T., Lipopolysaccharide from Actinobacillus actinomycetemcomitans stimulates production of interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-1 receptor antagonist in human whole blood, Journal of Periodontal Research, 34, 1, 1999. Crossref
-
Dhar Arun K., Thompson Margret S., Paradis Mary Rose, Alcivar-Warren Acacia, Determination of the cDNA sequence and mRNA expression of interleukin-1 receptor antagonist in horses, American Journal of Veterinary Research, 61, 8, 2000. Crossref
-
Luger T. A., Böhm M., Cytokines with Immunosuppressive Capacities, in Strategies for Immunointerventions in Dermatology, 1997. Crossref
-
Stoupis Athena, Zinner Stephen H., Approach to fever in the neutropenic host, in Management of Infectious Complications in Cancer Patients, 1998. Crossref
-
Daniel Vino, Anti-Inflammatory Activity, in Drug Discovery and Evaluation: Pharmacological Assays, 2016. Crossref
-
Vogel H. Gerhard, Vogel Wolfgang H., Schölkens Bernward A., Sandow Jürgen, Müller Günter, Vogel Wolfgang F., Analgesic, anti-inflammatory, and anti-pyretic activity1, in Drug Discovery and Evaluation, 2002. Crossref
-
Cytokines of the Immune Response, in Handbook of Imune Response Genes, 1998. Crossref
-
Daniel Vino, Anti-inflammatory Activity, in Drug Discovery and Evaluation: Pharmacological Assays, 2014. Crossref
-
Radeke Heinfried H., Resch Klaus, Molekulare Aspekte der chronischen Entzündung, in Immunsystem und Infektiologie, 1999. Crossref
-
Sauer J., Renner U., Hopfner U., Lange M., Müller A., Strasburger C. J., Pagotto U., Arzt E., Stalla G. K., Interleukin-1β Enhances Interleukin-1 Receptor Antagonist Content in Human Somatotroph Adenoma Cell Cultures1, The Journal of Clinical Endocrinology & Metabolism, 83, 7, 1998. Crossref
-
Holtkamp Gertjan M., de Vos Alex F., Kijlstra Aize, Peek Ron, Expression of multiple forms of IL‐1 receptor antagonist (IL‐1ra) by human retinal pigment epithelial cells: identification of a new IL‐1ra exon, European Journal of Immunology, 29, 1, 1999. Crossref
-
Smith Michael F., Carl Virginia S., Lodie Tracey, Fenton Matthew J., Secretory Interleukin-1 Receptor Antagonist Gene Expression Requires both a PU.1 and a Novel Composite NF-κB/PU.1/ GA-binding Protein Binding Site, Journal of Biological Chemistry, 273, 37, 1998. Crossref
-
Luhm Juergen, Langenkamp Ulrich, Hensel Jenny, Frohn Christoph, Brand Joerg M, Hennig Holger, Rink Lothar, Koritke Petra, Wittkopf Nadine, Williams David L, Mueller Antje, β-(1→3)-D-glucan modulates DNA binding of nuclear factors κB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1β/IL-1 receptor antagonist ratio, BMC Immunology, 7, 1, 2006. Crossref
-
Darragh Joanne, Ananieva Olga, Courtney Alan, Elcombe Suzanne, Arthur J. Simon C., MSK1 regulates the transcription of IL-1ra in response to TLR activation in macrophages, Biochemical Journal, 425, 3, 2010. Crossref
-
Arend William P., Malyak Mark, Guthridge Carla J., Gabay Cem, INTERLEUKIN-1 RECEPTOR ANTAGONIST: Role in Biology, Annual Review of Immunology, 16, 1, 1998. Crossref
-
Vijgen L, Van Gysel M, Rector A, Thoelen I, Esters N, Ceelen T, Vangoidsenhoven E, Vermeire S, Rutgeerts P, Van Ranst M, Interleukin-1 receptor antagonist VNTR-polymorphism in inflammatory bowel disease, Genes & Immunity, 3, 7, 2002. Crossref
-
ATRASHEUSKAYA A V, FREDEKING T M, IGNATYEV G M, Changes in immune parameters and their correction in human cases of tick-borne encephalitis, Clinical and Experimental Immunology, 131, 1, 2003. Crossref
-
Wong Ma-Li, Bongiorno Peter B., Rettori Valeria, McCann Samuel M., Licinio Julio, Interleukin (IL) 1β, IL-1 receptor antagonist, IL-10, and IL-13 gene expression in the central nervous system and anterior pituitary during systemic inflammation: Pathophysiological implications, Proceedings of the National Academy of Sciences, 94, 1, 1997. Crossref
-
Wang Catherine Y., Naka Yoshifumi, Liao Hui, Oz Mehmet C., Springer Timothy A., Gutierrez-Ramos Jose-Carlos, Pinsky David J., Cardiac Graft Intercellular Adhesion Molecule-1 (ICAM-1) and Interleukin-1 Expression Mediate Primary Isograft Failure and Induction of ICAM-1 in Organs Remote From the Site of Transplantation, Circulation Research, 82, 7, 1998. Crossref
-
Malyak Mark, Smith Michael F., Abel Ashley A., Hance Kenneth R., Arend William P., The Differential Production of Three Forms of IL-1 Receptor Antagonist by Human Neutrophils and Monocytes, The Journal of Immunology, 161, 4, 1998. Crossref
-
Malyak Mark, Guthridge Joel M., Hance Kenneth R., Dower Steven K., Freed John H., Arend William P., Characterization of a Low Molecular Weight Isoform of IL-1 Receptor Antagonist, The Journal of Immunology, 161, 4, 1998. Crossref