To investigate the presence and role of interleukin‐17 (IL‐17) in rheumatoid arthritis (RA), and its regulation by antiinflammatory cytokines.

The production of IL‐17 was measured in supernatants of RA, osteoarthritis (OA), and normal synovial tissue pieces cultured ex vivo. Quantification of IL‐17 was performed using a specific biologic assay. IL‐17 gene expression was investigated by reverse transcriptase–polymerase chain reaction (RT‐PCR)‐techniques. Immunohistochemistry was used to evaluate the frequency of IL‐17–positive cells in synovium. The secretion of IL‐17 by synovium was measured in the presence of IL‐4, IL‐13, and IL‐10. In addition, the contributions of exogenous and endogenous IL‐17 to IL‐6 production by RA synovium were studied.

Functional IL‐17 was spontaneously produced by 16 of 18 RA (mean ± SEM 41.7 ± 11.4 units/ml), 2 of 12 OA (5.3 ± 4.5 units/ml), and 0 of 3 normal synovial explant cultures. IL‐17 messenger RNA expression was demonstrated by RT‐PCR in 4 of 5 RA and 0 of 3 OA synovial samples. By immunostaining of RA synovium, IL‐17–producing cells were found in the T cell–rich area. Addition of both IL‐4 and IL‐13 completely inhibited the production of IL‐17, whereas IL‐10 had no effect. Addition of exogenous IL‐17 to RA synovium resulted in an increase in IL‐6 production, whereas that of a blocking anti–IL‐17 antibody reduced production of IL‐6.

The T cell cytokine IL‐17 was found to be highly produced by RA, but not by OA, synovium. Its production and function were down‐regulated by IL‐4 and IL‐13. These results indicate that IL‐17 contributes to the active, proinflammatory pattern that is characteristic of RA. Through the contribution of IL‐17, some Th1‐like T cells appear to mediate synovial inflammation.