Potential new targets in arthritis therapy: interleukin (IL)-17 and its relation to tumour necrosis factor and IL-1 in experimental arthritis.
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by chronic joint inflammation and destruction. Interleukin (IL)-17 is a T cell cytokine expressed in the synovium and synovial fluid of patients with RA. IL-17 is a potent inducer of various cytokines such as tumour necrosis factor (TNF) and IL-1. IL-17 has been shown to have additive or even synergistic effects with TNF and IL-1 during the induction of cytokine expression and joint damage in vitro and in vivo. TNFalpha and IL-1 are considered powerful targets in the treatment of RA because of their leading role in driving the enhanced production of cytokines, chemokines, and degradative enzymes. Besides anti-TNF and anti-IL-1 therapies, whose clinical efficacy is now established, new targets have been proposed for RA which is not responding to conventional treatments. This paper discusses the role of IL-17 in experimental arthritis and its interrelationship with TNF and IL-1, currently the most targeted cytokines in the treatment of RA. IL-17 is involved in both initiation and progression of murine experimental arthritis. Studies have shown that IL-17 not only synergises with TNF, but also enhances inflammation and destruction independent of IL-1 and TNF. On the basis of these studies, the authors propose IL-17 as an interesting additional target in the treatment of RA.
Koenders
M I
MI
Radboud University Nijmegen Medical Center, Department of Rheumatology, Rheumatology Research and Advanced Therapeutics, 272, Geert Grooteplein 26, PO Box 9101, 6500 HB Nijmegen, the Netherlands. m.koenders@reuma.umcn.nl
Joosten
L A B
LA
van den Berg
W B
WB
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D018450:Disease Progression; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000276:immunology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
D007375:Interleukin-1; D020381:Interleukin-17; D014409:Tumor Necrosis Factor-alpha