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From the Department of Rheumatology,* Experimental Rheumatology and Advanced Therapeutics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands; the Department of Pharmacology, Section AutoImmunity, Organon NV, Oss, The Netherlands; and the Novartis Institutes for Biomedical Research, Basel, Switzerland
Rheumatoid arthritis is characterized by an intermittent course of disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares. Here, we report that neutralizing endogenous IL-17 during reactivation of antigen-induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17 mRNA expression was clearly up-regulated during primary arthritis and was further enhanced after antigen rechallenge. Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a marker of osteoclast-like activity, and synovial RANKL mRNA expression were both suppressed. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial expression of both IL-1ß and tumor necrosis factor-
, whereas blocking IL-1 did not affect tumor necrosis factor- levels. These data indicate that IL-17 is an important upstream mediator in joint pathology during flare-up of experimental arthritis.
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