ROLE OF CHEMOKINES AND CYTOKINES IN A REACTIVATION MODEL OF ARTHRITISIN RATS INDUCED BY INJECTION WITH STREPTOCOCCAL CELL-WALLS

Intraarticular injection of streptococcal cell wall(SCW) antigen follo wed by intravenous challenge results in a T cell-mediated monoarticula r arthritis iu female Lewis rats. Initial studies showed that this rea ctivation response to intravenous SCW antigen is dependent on the pres ence of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alph a) and that the early phase of swelling is neutrophil-dependent. Neutr ophil depletion or passive immunization with antibodies to P-selectin or macrophage inflammatory protein-2 reduced the intensity of ankle ed ema and the influx of neutrophils, After the first few days, however, the arthritic response is mediated primarily by mononuclear cells, Joi nt tissues showed up-regulation of mRNA for monocyte chemotactic prote in-1 (MCP-1), which could be inhibited in part by anti-IL-4; treatment of rats with antibodies to IL-4 or MCP-1 significantly suppressed dev elopment of ankle edema and histopathological evidence of inflammation , Antibodies to interferon-gamma or IL-10 had no effect, Treatment wit h anti-MCP-1 also suppressed influx of In-111-labeled T cells into the ankle joint, These data suggest that the late, mononuclear-dependent phase of SCW-induced arthritis in female Lewis rats requires cytokines that up-regulate MCP-1, which in turn may facilitate recruitment and extravasation of mononuclear cells into the joint.