Macrophage Migration Inhibitory Factor Induces Il-8 Productionin Synovial Fibroblasts of Rheumatoid Arthritis

INTRODUCTION Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by severe synovitis and cartilage destruction. Synovial cells play a major role in the pathogenesis of RA through the synthesis of various cytokines, proteases, superoxide, etc. Interleukin-8 (IL-8), one of CXC chemokines, is known to recruit neutrophils into inflammatory loci. Chemokines have been reported to be highly expressed within the RA inflammatory synovium, mainly produced by macrophages, fibroblasts, and endothelial cells within the synovium, induced by proinflammatory cytokines such as IL-1 or TNF-alpha, and considered to participate in the inflammatory process at an early stage of RA. We already reported that macrophage migration inhibitory factor (MIF), which has recently been re-evaluated as a mediator in various inflammatory diseases, is exclusively expressed in CD45+ T cells of rheumatoid synovium, and that the concentrations of MIF in the joint fluids are much higher in RA patients than in osteoarthritis (OA) patients or nomal volunteers [1]. We also reported that MIF is a potent inducer of matrix metalloproteinases (MMPs) in rheumatoid synovial fibroblasts [2]. However, the role of MIF in RA still remains unelucidated. In this study, we investigated the effect of MIF on the rheumatoid synovial fibroblasts from the viewpoint of IL-8 induction.