Human interleukin-17 - A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium

Objective, To investigate the presence and role of interleukin-17 (IL-17) i n rheumatoid arthritis (RA), and its regulation by antiinflammatory cytokin es, Methods. The production of IL-17 was measured in supernatants of RA, osteoa rthritis (OA), and normal synovial tissue pieces cultured ex vivo, Quantifi cation of IL-17 was performed using a specific biologic assay, IL-17 gene e xpression was investigated by reverse transcriptase-polymerase chain reacti on (RT-PCR)-techniques. Immunohistochemistry was used to evaluate the frequ ency of IL-17-positive cells in synovium, The secretion of IL-17 by synoviu m 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 sy novium were studied. Results. 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 o f 3 normal synovial explant cultures. IL-17 messenger RNA expression was de monstrated by RT-PCR in 4 of 5 RA and 0 of 3 OA synovial samples. By immuno staining of RA synovium, IL-17-producing cells were found in the T cell-ric h 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 s ynovium resulted in an increase in IL-6 production, whereas that of a block ing anti-IL-17 antibody reduced production of IL-6, Conclusion. 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 act ive, proinflammatory pattern that is characteristic of RA. Through the cont ribution of IL-17, some Th1-like T cells appear to mediate synovial inflamm ation.