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

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-gamma.

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.