A comparison of immunosuppressive and anti-inflammatory agents in the rat

Abstract

The action of four anti-proliferative agents: azathioprine, chlorambucil, cyclophosphamide and methotrexate have been studied in the rat and compared with the actions of phenylbutazone, hydrocortisone and anti-lymphocyte serum. All the anti-proliferative drugs effectively inhibited adjuvant arthritis. Therapeutic/toxic ratios were most favourable with cyclophosphamide, least favourable with azathioprine. In somewhat higher doses than those needed to inhibit adjuvant arthritis, the anti-proliferative drugs suppressed both the primary antibody response to sheep erythrocytes and the tuberculin skin test, and reduced the inflammatory paw swelling 48 hr after an injection of Freund's complete adjuvant. Anti-lymphocyte serum produced effects very similar to the anti-proliferative agents, including the anti-inflammatory effect. The results suggest that the inhibition of delayed hypersensitivity responses to tuberculin in rats receiving cyclophosphamide may represent a predominantly anti-inflammatory, rather an immunosuppressive, effect.