INTERLEUKIN-10 COOPERATES WITH INTERLEUKIN-4 TO SUPPRESS INFLAMMATORY CYTOKINE PRODUCTION BY FRESHLY PREPARED ADHERENT RHEUMATOID SYNOVIAL-CELLS

Objective. Inflammatory cytokines have been implicated as important mediators of inflammation in rheumatoid arthritis (RA). We investigated whether interleukin 4 (IL-4) and interleukin 10 (IL-10) suppress the production of inflammatory cytokines by freshly prepared adherent rheumatoid synovial cells. Methods, Adherent synovial cells were obtained from the rheumatoid synovium by collagenase digestion. The levels of IL-1B, tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 in culture supernatants were measured by ELISA. The gene expressions of IL-6 and IL-8 were determined by Northern blot analysis. Results, Freshly prepared rheumatoid synovial cells spontaneously produced large amounts of IL-6 and IL-8. However, the amounts of IL-1B and TNF-alpha produced were similar to 1000-fold less than those of IL-6 and IL-8. IL-4 alone inhibited the production of IL-1B, IL-6, and IL-8 by 32, 35, and 50%, respectively. IL-10 alone was less potent than IL-4 in suppressing these cytokines, Of note, the combination of IL-4 and IL-10 cooperatively exerted potent suppressive effects on the production of IL-1B, IL-6, and IL-8 by 74.3, 69, and 77%, respectively. The suppressive effects of the combination of IL-4 and IL-10 on IL-6 and IL-8 were also observed at the levels of mRNA. Conclusion, These results suggest the combination of IL-4 and IL-10 may be capable of suppressing the production of inflammatory cytokines at rheumatoid inflammatory joints.