DIFFERENTIAL INHIBITORY EFFECTS OF INDOMETHACIN, DEXAMETHASONE, AND INTERFERON-GAMMA (IFN-GAMMA) ON IL-11 PRODUCTION BY RHEUMATOID SYNOVIAL-CELLS

IL-11, a member of the IL-6 type cytokines, has some biological activi ty related to the joint destruction in rheumatoid arthritis (RA), such as induction of osteoclast differentiation. However, its expression a nd regulation in rheumatoid inflamed joints has not been clarified. In the present study we examined the capacity of fresh rheumatoid synovi al cells (fresh RSC) to produce IL-11, and the effect of indomethacin, dexamethasone and IFN-gamma on IL-11 production. Fresh RSC obtained f rom eight patients with RA produced large amounts of IL-11, measured b y ELISA, and showed strong expression of IL-11 mRNA, determined by Nor thern blotting. Indomethacin inhibited the production of IL-11 by abou t 55%. Prostaglandin E-2 (PGE(2)) completely prevented the inhibition, suggesting that IL-11 production by fresh RSC was in part mediated by PGE(2). Dexamethasone inhibited the production of IL-11 by more than 80%. Interestingly, the inhibition was not abolished by PGE(2). IFN-ga mma inhibited the production of IL-11 from IL-1 alpha-stimulated cultu red rheumatoid synovial fibroblasts, although IFN-gamma did not inhibi t the production of IL-11 by fresh RSC. These results suggest that the production of IL-11 by rheumatoid synovia was differentially regulate d by PGE(2) and IFN-gamma, and that treatment with indomethacin or dex amethasone decreased the level of IL-11 at inflammatory joints in pati ents with RA.