Immunosuppressive agents in chronic severe asthma.

Abstract

Previous immunosuppressive agents utilized as therapies for immune system mediated diseases such as chronic allergic asthma, and rheumatoid arthritis include purine antagonists, methotrexate, and gold salts. These treatment modalities have been shown to elicit either limited treatment efficacy or to produce undesirable side effects in many individuals. Cyclosporin A is a potent immunosuppressive agent which appears to arrest division of T lymphocytes and inhibit mediator release from mast cells. However, like other immunosuppressive agents, cyclosporin A may also produce many potentially serious side effects; among these is the possibility of irreversible renal damage. Nephrotoxicity can be attenuated, because renal pathological changes seem to be high cumulative dose-related. If whole blood levels of cyclosporin A are maintained between 200 and 500 ng/mL, serious renal toxicity is unusual. Investigation of cyclosporin A in individuals who have severe long-term corticosteroid-dependent chronic asthma has demonstrated the efficacy of this agent, resulting in clinically significant improvement in pulmonary function. Therefore, it can be hypothesized that T lymphocytes may act as effector cells in cell-mediated hypersensitivity reactions in atopic allergic inflammation.