INTERLEUKIN-10 FUNCTIONS AS AN ANTIINFLAMMATORY CYTOKINE IN RHEUMATOID SYNOVIUM

Objective. Interleukin-10 (IL-10) is an antiinflammatory cytokine that has been shown to play a role in rheumatoid arthritis (RA). We theref ore investigated the effects of IL-10 on the function and phenotype of synovial fluid mononuclear cells (SFMC) derived from patients with RA . In addition, we studied the production of IL-10 in rheumatoid joints , and the role of endogenous IL-10 in the regulation of SFMC function. Methods. The presence of IL-10 in rheumatoid joints was studied using IL-10-specific enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. The effec ts of recombinant human IL-10 or neutralizing anti-IL-10 monoclonal an tibodies (MAbs) on both cytokine production and phenotype of SFMC were evaluated using cytokine-specific ELISAs and how cytometry. The effec t of IL-10 on proliferation of SFMC was determined by incorporation of tritiated thymidine. Results. IL-10 was detected by ELISA in 22 of 23 SF samples, and was spontaneously produced by cultured SFMC. IL-10 me ssenger RNA was detectable in all 8 SFMC samples, as determined by RT- PCR. Neutralization of endogenously produced IL-10 by anti-IL-10 MAbs resulted in increased production of IL-1 beta, tumor necrosis factor a lpha (TNF alpha), and granulocyte- macrophage colony-stimulating facto r (GM-CSF) by SFMC, and in enhanced proliferation of SFMC. In particul ar, the production of TNF alpha was dramatically increased by anti-IL- 10 MAbs. Moreover, the expression of HLA-DR molecules by SF macrophage s was increased, and the expression of CD16 was decreased by anti-IL-1 0 MAbs. In contrast, addition of recombinant IL-10 significantly decre ased the production of IL-1 beta, TNF alpha, and GM-CSF by SFMC, and d ecreased spontaneous and IL-2-induced proliferation of SFMC. Finally, IL-10 decreased HLA-DR expression and increased the expression of the Fc gamma receptors, CD16 and CD64, by SF macrophages. Conclusion. Thes e data indicate that endogenously produced IL-10 functions as an immun oregulatory molecule in rheumatoid synovium. Importantly, exogenous IL -10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.