Interleukin-10 inhibits the capacity of synovial macrophages to function as antigen-presenting cells

Objective. We have investigated the effects of interleukin (IL)-10, IL-4 granulocyte/macrophage colony-stimulating factor (GM-CSF) and tumour necros is factor alpha (TNF-alpha) on the phenotype and antigen-presenting capacit y of synovial fluid (SF) macrophages from patients with rheumatoid arthriti s. Methods. The effects of IL-4, IL-10, GM-GSF and TNF-alpha on the expression of surface antigens on SF macrophages were studied using flow cytometry. T he effects of these cytokines on the capacity of SF macrophages to activate T cells was investigated using the allogeneic mixed lymphocyte reaction (M LR), Results. IL-10 reduced the expression of CD40, CD86 and HLA-DR, and increas ed the expression of CD14, on SF macrophages. IL-IO had no effect on the ex pression of CD80. Importantly, these effects of IL-10 on the phenotype of S F macrophages appear to have functional consequences, because cells incubat ed with IL-10 had a significantly reduced capacity to activate T cells in M LR. The effects of IL-4, GM-CSF and TNF-alpha were generally opposite to th ose observed in response to IL-10. IL-4 + GM-CSF, a combination of cytokine s known to induce differentiation of dendritic cells, increased the express ion of CD40, CD80 and CD86, and decreased the expression of CD14 on SF macr ophages. Accordingly, IL-4 + GM-CSF increased the capacity of SF macrophage s to activate T cells in MLR. IL-10 inhibited the effects of IL-4 + GM-GSF on SF macrophages. Conclusions. IL-10 inhibits the antigen-presenting capacity of SF macrophag es, which further emphasizes the anti inflammatory potential of IL-10 in RA . Importantly, IL-10 is able to downregulate the APC function of SF macroph ages even when they are efficiently activated.