Differential effects of interleukins 10 and 4 on the production of interleukin‐6 by blood and synovium monocytes in rheumatoid arthritis

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Abstract
Objective. To determine how the antiinflammatory cytokines interleukin‐10 (IL‐10) and IL‐4 affect the production of IL‐6 in rheumatoid arthritis (RA) and to assess the contribution of IL‐10 production.Methods. IL‐6 production was measured by enzyme‐linked immunosorbent assay (ELISA) in the supernatants of cultured RA synovium pieces (from 23 patients), purified RA synovial tissue monocyte/macrophages, and RA blood monocytes, in the presence of IL‐10 and IL‐4. IL‐10 was also detected by ELISA in culture supernatants and in RA sera.Results. The production of IL‐6 by RA synovium was strongly inhibited by IL‐4 (46.6%; P = 0.0001) and was inhibited to a lower extent by IL‐10 (25.3%; P = 0.03). Likewise, the spontaneous production of IL‐6 by RA synovial tissue monocyte/macrophages was decreased by the addition of IL‐4 (48.8%) and IL‐10 (23.7%). This inhibition of IL‐6 production was significantly lower (P < 0.03) than that observed with RA blood monocytes (83.0% for IL‐10 and 85.2% for IL‐4). Interestingly, and in contrast to RA blood monocytes, RA synovial tissue monocyte/macrophages produced spontaneously high levels of IL‐10, which were inhibited by IL‐4 and interferon‐γ.Conclusion. The ability of IL‐10 and IL‐4 to suppress IL‐6 production was dependent on 1) differences in the state of differentiation of blood and synovial tissue monocytes, and 2) local production of cytokine inside the synovium.

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