Contribution of interleukin 17 to human cartilage degradation and synovial inflammation in osteoarthritis

Objective: To compare the effect of interleukin (IL)-17, IL-1beta and TNF-alpha on chemokine production by human chondrocytes and synovial fibroblasts isolated from patients with osteoarthritis (OA). The expression of IL-1beta mRNA by OA chondrocytes was also assessed, as well as the presence and expression of IL-17 receptor (IL-17R) in OA chondrocytes and synovial fibroblasts after stimulation with IL-17, IL-1beta and TNF-alpha. Design: Synovial fibroblasts and chondrocytes isolated from patients with OA were stimulated in vitro with IL-17, IL-1beta or TNF-alpha. Supernatants were collected and immunoassayed for the presence of IL-8, GRO-alpha (CXC chemokines) and MCP-1, RANTES (CC chemokines). The cells were used to detect the presence of IL-17R and the expression of IL-17R mRNA. Stimulated chondrocytes were also used to detect IL-1beta production and mRNA expression. Results: IL-17 upregulated the release of IL-8 and GRO-alpha both by synovial fibroblasts and chondrocytes, and the release of MCP-1 only by chondrocytes. IL-17 was a weaker stimulator than IL-1beta and TNF-alpha, except for GRO-alpha release which was maximally upregulated by IL-1beta, less by IL-17 and minimally by TNF-alpha. When compared to IL-1beta, IL-17 was more active on chondrocytes than on fibroblasts. In chondrocytes the expression of IL-1beta mRNA was enhanced by IL-17 and TNF-alpha, with a maximum level reached by IL-1beta. IL-17 and TNF-alpha stimulated IL-1beta release in few subjects. Neither IL-17, IL-1beta nor TNF-alpha modulated the presence of IL-17R and the expression of IL-17R mRNA. Conclusions: These data suggest that IL-17 could contribute to cartilage breakdown and synovial infiltration in OA by inducing both the release of chemokines by chondrocytes and synovial fibroblasts and, in a less extent, the synthesis of IL-1beta by chondrocytes. (C) 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd. All rights reserved.