Role of cytokines in rheumatoid synovitis

Although the chronic inflammatory reaction in rheumatoid synovitis appears to be stimulated by an as yet unidentified antigen, the mononuclear cell infiltration is to a large extent accomplished through the nonspecific action of cytokines and growth factors acting as (1) chemotactic agents for the emigration and ecotaxis of monocytes and lymphocytes, (2) upregulators of endothelial cells for the binding of lymphocytes and monocytes to the endothelium of postcapillary venules prior to emigration and (3) angiogenic agents for the proliferation of the microvasculature, and as a result, the proliferation of the synovial membrane. The synovial lining layer may play an important part in this process by stimulating the infiltration of the synovial tissue with "exudate macrophages" as a necessary step in the development of lining layer hyperplasia. Evidence for the capacity of the cytokines to mediate chronic synovitis is provided by the well-known observation that intraarticular injection of cytokines, particularly IL-1, produces both acute and chronic synovitis in the experimental animal.