Strategies for Specific Immunosuppression in Vitro with Cyclosporine

Abstract

Cyclosporine A (CsA) represents a class of immunosuppressive drug distinct from those in common clinical use such as cytotoxic drugs, steroids, and antilymphocyte globulins. CsA is under investigation for treatment of various autoimmune disorders including multiple sclerosis, myasthenia gravis, and diabetes mellitus Type 1 (reviewed in reference 1). Most notable, however, is its use in immunosuppressive therapy for organ transplant recipients, and the agent is now included in most protocols to prevent graft rejection, generally in conjunction with azathioprine or prednisone. Table 5.1 summarizes the history of immunosuppressive therapy. While CsA remains an important drug in many immunotherapeutic protocols, several major problems are associated with long-term exposure to CsA. Primarily, there is irreversible and potentially progressive renal damage, and a global immune suppression resulting in increased susceptibility to opportunistic infections and lymphomas. Other problems associated with CsA administration, which are less prevalent but still significant, are hepatotoxicity, respiratory distress, convulsions, and damage to other organs including skin and bone marrow (2–11).