Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / therapeutic use
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Antibody Formation
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Arthritis, Experimental / genetics
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / physiopathology*
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Arthritis, Rheumatoid / therapy
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Autoimmune Diseases / immunology
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Autoimmune Diseases / physiopathology*
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Autoimmune Diseases / therapy
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Chondrocytes / metabolism
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Cysteine Endopeptidases / physiology
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Cytokines / physiology
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Humans
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Immunity, Cellular
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Infections / immunology
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Inflammation / physiopathology
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Interleukin-18 / antagonists & inhibitors
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Interleukin-18 / deficiency
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Interleukin-18 / genetics
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Interleukin-18 / physiology*
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Interleukin-18 Receptor alpha Subunit
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Membrane Glycoproteins / drug effects
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Membrane Glycoproteins / physiology
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Mice
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Mice, Knockout
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Models, Immunological
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Neoplasms / immunology
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Osteoarthritis / immunology
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Osteoarthritis / physiopathology*
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Osteoarthritis / therapy
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Receptors, Cell Surface / drug effects
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Receptors, Cell Surface / physiology
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Receptors, Interleukin / drug effects
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Receptors, Interleukin / physiology
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Receptors, Interleukin-18
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Signal Transduction / physiology
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Synovial Membrane / metabolism
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Th1 Cells / immunology
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Th2 Cells / immunology
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha / physiology
Substances
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Antibodies, Monoclonal
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Cytokines
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IL18R1 protein, human
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Il18r1 protein, mouse
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Interleukin
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Receptors, Interleukin-18
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Toll-Like Receptors
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Tumor Necrosis Factor-alpha
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Cysteine Endopeptidases