Cytokine expression in rheumatoid synovium: Is rheumatoid arthritis a Th 1 cell-mediated autoimmune disease?

Rheumatoid arthritis (RA) is a chronic inflammatory disease of multiple joints involving autoimmunity. Despite the abundance of inflammatory cytokines produced by macrophages and fibroblast-like cells, T cell cytokines have been identified at very low levels in the synovium of RA. However, increasing evidence has recently indicated that RA is mediated by Th 1 cells capable of producing high levels of IFN-γ. We found that IL-12, produced by RA synovial macrophages, increased the level of IFN-γ production by synovium-infiltrating T cells and maintained the potential for driving their cytokine response towards a Th 1 phenotype, indicating an important role of IL-12 in perpetuating Th 1 type immune responses in chronic RA. We also found that fibroblast lines isolated from RA synovium were able to produce the cytokines IL-7 and IL-15, which could stimulate the local expansion of T cells. We discuss here the possible involvement of Th 1 cells in the pathogenesis of RA from the viewpoint of local cytokine expression.