Interleukin 17 synergises with tumour necrosis factor α to induce cartilage destruction in vitro

Abstract

Background: Interleukin 17 (IL17) is produced by activated T cells and has been implicated in the development of bone lesions and cartilage degradation in rheumatoid arthritis (RA). Objective: To determine whether IL17, alone or together with tumour necrosis factor α (TNFα), induces cartilage destruction in vitro. Methods: Fetal mouse metatarsals stripped of endogenous osteodast precursors were used to study the effect of IL17 on cartilage degradation independently of osteoclastic resorption. Cartilage destruction was analysed histologically by Alcian blue staining. Results: IL17 alone, up to 100 ng/ml, had no effect on the cartilage of fetal mouse metatarsals. IL17 (≥0.1 ng/ml), however, induced severe cartilage degradation when given together with TNFα (≥1 ng/ml). The cytokine combination decreased Alcian blue staining, a marker of proteoglycans, throughout the metatarsals and induced loss of the proliferating and early hypertrophic chondrocyte zones. TNFα alone also decreased Alcian blue staining, but not as dramatically as the cytokine combination. In addition, it did not induce loss of chondrocyte zones. Treatment with inhibitors of matrix metalloproteinase (MMP) activity and nitric oxide synthesis showed that MMP activity played a part in cartilage degradation, whereas nitric oxide production did not. Conclusions: IL17, together with TNFα, induced cartilage degradation in fetal mouse metatarsals in vitro. IL17 may, therefore, participate in the development of cartilage destruction associated with RA by enhancing the effects of TNFα and may provide a potential therapeutic target.