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

D. J. Schrier, R. C. Schimmer, C. M. Flory, D. K.L. Tung, P. A. Ward

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Intraarticular injection of streptococcal cell wall (SCW) antigen followed by intravenous challenge results in a T cell-mediated monoarticular arthritis in 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 α (TNF-α) 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-γ or IL-10 had no effect. Treatment with anti-MCP-1 also suppressed influx of 111In-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.

Original languageEnglish (US)
Pages (from-to)359-363
Number of pages5
JournalJournal of Leukocyte Biology
Volume63
Issue number3
DOIs
StatePublished - Mar 1998

Keywords

  • Interleukin-1
  • Mononuclear cells
  • Tumor necrosis factor α

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