Inhibition by cyclosporin A of streptococcal cell wall‐induced arthritis and hepatic granulomas in rats

Abstract

We investigated the effect of cyclosporin A, an inhibitor of T helperhnducer lymphocyte activation, on the dtwelopment of streptococcal cell wall-induced arm thritis 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 str'eptococcal cell wall antigen distribution or persistence in tissues. These data provide additional evidence of an important role for the T helperhnducer lymphocyte in the experimental model and suggest that cyFrom the Arthritis and Rheumatism Branch, National Institute (of Arthritis, Diabetes, and Digestive and Kidney Diseases,

Bacterial cell wall-induced immunosuppression. Role of transforming growth factor beta.

“…Evaluation of lymphocyte function at various time points after SCW administration revealed that within 18 h the proliferative response was suppressed . This immune-deficient state continued through the development of acute arthritic symptoms (days [3][4][5] and persisted during the evolution of the chronic erosive joint lesions (>3 wk) (Fig. 2).…”

Gut flora induces and maintains resistance against streptococcal cell wall-induced arthritis in F344 rats

“…However, functional T lymphocytes have been shown to play a pivotal role in suseeptibility to SCWinduced, chronic joint inflammation; there even is evidence that SCW-specific T cells are required [3][4][5][6][8][9][10][11]17], Thus, an answer to the question why T cells from F344 rats do not respond to SCW after priming with cell walls might elucidate the mechanism of resistance to SCW arthritis.…”

“…Dependent on the SCW batch used, either biphasic disease or only the chronic phase may be seen, Thymectomized [3,4], cyclosporin A-treated [4,5] or nude Lewis rats [6], as well as F344 rats [7] are resistant to the second, destructive episode of inflammation, whereas they undergo the acute phase with comparable severity to the Lewis rat. Together, these data strongly suggest an absolute dependence on functional T lymphocytes of the ehronic phase of SCW-induced arthritis.…”

Chimeric cytotoxin IL2-PE40 delays and mitigates adjuvant-induced arthritis in rats.

“…Arthritis was uniformly detected in control cohorts by day 11. Clinical scoring of arthritis was performed as described (22). The distal parts of the fore-and hindlimbs of each animal were graded for swelling on a score of 0-4, ranging from none to maximal involvement.…”