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 ill 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 (111)In-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.
Schrier
D J
DJ
Department of Immunopathology, Parke-Davis Pharmaceutical Research/Division of Warner Lambert Company, Ann Arbor, MI 48105, USA.
Schimmer
R C
RC
Flory
C M
CM
Tung
D K
DK
Ward
P A
PA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D002473:Cell Wall / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D054426:Chemokine CXCL2; D002630:Chemotactic Factors / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D004487:Edema; D005260:Female; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D007596:Joints / Q000276:immunology / Q000473:pathology; D015846:Monokines / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D019007:P-Selectin / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D013291:Streptococcus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D000906:Antibodies; D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D002630:Chemotactic Factors; D016207:Cytokines; D015846:Monokines; D019007:P-Selectin; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma