Pathophysiological roles for IL-18 in inflammatory arthritis.
IL-18 is a unique cytokine with prominently wide spectrum biological actions. Among these, its IFN-gamma/TNF-alpha-inducing activity primarily contributes to the development of various inflammatory diseases including inflammatory arthritis. IL-18 levels correlate with the disease activity of rheumatoid arthritis (RA) and osteoarthritis (OA). IL-18 is spontaneously released from RA synovial cells and OA chondrocytes and seems to participate in the development of the inflammatory and destructive alterations of joints via induction of TNF-alpha, a potent effector molecule. TNF-alpha, in turn, increases IL-18 expression in RA synovial cells. Recent clinical trials have revealed the efficacy of TNF-alpha in RA with a reduction in circulatory IL-18 levels. These may implicate the positive circuit between IL-18 and TNF-alpha for development of RA. As IL-18-deficient mice evade collagen-induced arthritis in a mouse RA model, therapeutics targeting IL-18 may be beneficial against RA/OA. Here, the authors review the possible roles of IL-18 in inflammatory arthritis.
Matsui
Kiyoshi
K
Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan.
Tsutsui
Hiroko
H
Nakanishi
Kenji
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D019902:Chondrocytes / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000502:physiology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007239:Infections / Q000276:immunology; D007249:Inflammation / Q000503:physiopathology; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology; D010003:Osteoarthritis / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D018123:Receptors, Interleukin / Q000187:drug effects / Q000502:physiology; D053724:Receptors, Interleukin-18; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D000911:Antibodies, Monoclonal; D016207:Cytokines; C508572:IL18R1 protein, human; C508573:Il18r1 protein, mouse; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D003546:Cysteine Endopeptidases