Inhibition by cyclosporin A of streptococcal cell wall-induced arthritis and hepatic granulomas in rats.
We investigated the effect of cyclosporin A, an inhibitor of T helper/inducer lymphocyte activation, on the development of streptococcal cell wall-induced arthritis and hepatic granulomas in female LEW/N rats. Continuous daily treatment with cyclosporin A, begun either 24 hours before or 7-12 days after streptococcal cell wall administration and continued for 6 weeks, resulted in significant inhibition of the chronic proliferative, erosive synovitis and total inhibition of hepatic granuloma formation. When cyclosporin A was stopped at 6 weeks, its effects continued for at least another 5 weeks, demonstrating long-term benefit without continued administration of the drug. In contrast, therapy given only during the acute phases of the experimental disease (days 1-12) did not inhibit the development of chronic disease. Cyclosporin A had no apparent effects on streptococcal cell wall antigen distribution or persistence in tissues. These data provide additional evidence of an important role for the T helper/inducer lymphocyte in the experimental model and suggest that cyclosporin A may be a useful probe in defining molecular and cellular processes involved in chronic proliferative and erosive synovitis.
D000818:Animals; D000942:Antigens, Bacterial / Q000032:analysis; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D003524:Cyclosporins / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006099:Granuloma / Q000473:pathology / Q000517:prevention & control*; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D013297:Streptococcus pyogenes / Q000276:immunology*; D013585:Synovitis / Q000517:prevention & control; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D000942:Antigens, Bacterial; D003524:Cyclosporins