Expression of interleukin 10 mRNA and protein by synovial fibroblastoid cells

Objective. To determine if fibroblast-like synoviocytes (FLS) express inter leukin 10 (IL-10) mRNA and protein and functional IL-10 receptors. Methods. The pattern of IL-10 production was analyzed in inflammatory synov ial tissues by immunohistochemistry. Expression of IL-10 mRNA and protein w as determined by Northern blot analysis and ELISA in resting FLS and follow ing stimulation with IL-1 beta and tumor necrosis factor-alpha (TNF-alpha). IL-10 receptor expression was measured on cultured FLS by immunohistochemi stry and FAGS analysis after treatment with biotinylated IL-10. Responsiven ess of FLS to IL-10 was determined by multigene assay and inhibition of pro staglandin E-2 induced morphologic changes. Bioactivity was confirmed by do wnregulation of interferon-gamma stimulated HLA-DR expression by FAGS and i nhibition of TNF-alpha production by U937 cells. Results. Using immunohistochemistry. we detected IL-10 in the lining layer of inflamed synovial tissue and FLS. ELISA on unstimulated third passage FL S culture supernatants revealed lL-10 production that varied over time and among cell lines. FLS produced IL-10 mRNA constitutively. IL-10 production was upregulated by IL-1 beta and TNF-alpha. IL-10 bound to receptors on FLS and induced functional changes. Endogenously released FLS IL-10 was biolog ically active. Conclusion. Mesenchymal lining cells in the inflamed joint produce IL-10. I n addition, cultured FLS constitutively produce IL-10 mRNA and protein that is bioactive and can be upregulated by IL-1 beta and TNF-alpha. FLS expres s functional IL-10 receptors. These results suggest that IL-10 released by mesenchymal cells in inflammatory arthritis can modulate synovial inflammat ion and joint destruction by paracrine and/or autocrine mechanisms.