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The Journal of Immunology, 1998, 160: 1466-1471.
Copyright © 1998 by The American Association of Immunologists

Streptococcal Cell Wall-Induced Arthritis: Requirements for IL-4, IL-10, IFN-{gamma}, and Monocyte Chemoattractant Protein-11

Ralph C. Schimmer*,{dagger},¶, Denis J. Schrier2,{dagger}, Craig M. Flory{dagger}, Keith D. Laemont{dagger}, David Tung{dagger},¶, Alan L. Metz{ddagger}, Hans P. Friedl*, Mary Carol Conroy{dagger}, Jeffrey S. Warren, Beatrice Beck§,¶ and Peter A. Ward

* Department of Surgery, University of Zurich Medical School, Zurich, Switzerland; {dagger} Department of Immunopathology and {ddagger} Toxicology, Parke-Davis Pharmaceutical Research/Division of Warner Lambert Co., Ann Arbor, MI 48105; § Institute for Anesthesiology, University of Zurich Medical School, Zurich, Switzerland; and Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109

Intra-articular injection of streptococcal cell wall Ag followed by i.v. challenge ("reactivation") results in a destructive lymphocyte-dependent monoarticular arthritis. To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were evaluated. Treatment of rats with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti-IFN-{gamma} either had no effect or slightly enhanced the inflammatory response. These results suggest that 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 evaluated. Initial studies demonstrated that mRNA (as determined by in situ hybridization) and protein (as determined by immunofluorescence) for MCP-1 were detectable in inflamed synovial tissue in a time-dependent 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 111In-labeled T cells. These data suggest that the reactivation model of streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1.




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