Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with Streptococcal cell walls

Intraarticular injection of streptococcal cell wall(SCW) antigen followed by intravenous challenge results in a T cell-mediated monoarticular arthritis iu female Lewis rats. Initial studies showed that this reactivation response to intravenous SCW antigen is dependent on the presence of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and that the early phase of swelling is neutrophil-dependent. Neutrophil depletion or passive immunization with antibodies to P-selectin or macrophage inflammatory protein-2 reduced the intensity of ankle edema and the influx of neutrophils, After the first few days, however, the arthritic response is mediated primarily by mononuclear cells, Joint tissues showed up-regulation of mRNA for monocyte chemotactic protein-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 development of ankle edema and histopathological evidence of inflammation, Antibodies to interferon-gamma or IL-10 had no effect, Treatment with 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.