STREPTOCOCCAL CELL WALL-INDUCED ARTHRITIS - REQUIREMENTS FOR IL-4, IL-10, IFN-GAMMA, AND MONOCYTE CHEMOATTRACTANT PROTEIN-1

Intra-articular injection of streptococcal cell wall Ag followed by i. v. challenge (''reactivation'') results in a destructive lymphocyte-de pendent monoarticular arthritis, To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were eva luated, Treatment of rats with antibodies to IL-4 reduced swelling, wh ile treatment with anti-IL-10 or anti-IFN-gamma either had no effect o r slightly enhanced the inflammatory response, These results suggest t hat Th-2 immune mechanisms may be, at least in part, operative in the model, To more precisely define the role of IL-4, the effects of anti- IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were eva luated. Initial studies demonstrated that mRNA (as determined by in si tu hybridization) and protein (as determined by immunofluorescence) fo r MCP-1 were detectable in inflamed synovial tissue in a time-dependen t manner, Anti-IL-4 treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h after reactivation, In addition, anti-MCP-1 inhibited swelling and reduced influx of In-111-labeled T cells, Thes e data suggest that the reactivation model of streptococcal cell wail Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1.