Abstract
Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes. High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however, IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-alpha, IL-1, and receptor activator of NF-kappaB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-alpha in inducing cytokine expression and joint damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17 has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17 cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy.
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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Antirheumatic Agents / pharmacology
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Antirheumatic Agents / therapeutic use
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Arthritis, Experimental / drug therapy
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Arthritis, Experimental / pathology
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Arthritis, Experimental / physiopathology*
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Arthritis, Rheumatoid / drug therapy
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Arthritis, Rheumatoid / etiology*
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Arthritis, Rheumatoid / pathology
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Arthritis, Rheumatoid / physiopathology
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Autoimmune Diseases / physiopathology
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Bone and Bones / pathology
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Carrier Proteins / physiology
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Cartilage, Articular / pathology
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Cytokines / biosynthesis
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Cytokines / genetics
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Gene Expression Regulation / physiology
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Humans
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Inflammation / physiopathology
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Interleukin-17 / antagonists & inhibitors
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Interleukin-17 / physiology*
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Interleukins / physiology
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Membrane Glycoproteins / physiology
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Mice
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Neutrophils / pathology
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Osteoclasts / pathology
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RANK Ligand
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Rats
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Interleukin / physiology
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Receptors, Interleukin-17
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Species Specificity
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Synovial Fluid / metabolism
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T-Lymphocytes / metabolism*
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Tumor Necrosis Factor-alpha / physiology
Substances
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Antirheumatic Agents
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Carrier Proteins
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Cytokines
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IL17RA protein, human
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Il17ra protein, mouse
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Interleukin-17
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Interleukins
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Membrane Glycoproteins
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Interleukin
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Receptors, Interleukin-17
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TNFRSF11A protein, human
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TNFSF11 protein, human
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Tnfrsf11a protein, mouse
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Tnfsf11 protein, mouse
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Tumor Necrosis Factor-alpha