Molecular Mechanisms of Cyclosporin A

Abstract

Since it was first introduced into clinical medicine in the middle of 1978, the fungal metabolite cyclosporin A has become the standard drug in the management of organ and bone marrow transplantation [1]. In the treatment of various autoimmune diseases the immunosuppressive agent has also proven effective in uveitis and Behçet’s disease [2]. Cyclosporin A can cause several side effects, among which nephro- and hepatotoxicity are of most concern. As this toxicity is more pronounced when these organs are already affected by the underlying disease, its use in more generalized autoimmune or chronic inflammatory diseases such as lupus erythematosus or rheumatoid arthritis so far is limited [3]. Finding approaches for minimizing the unwanted side effects while retaining the immunosuppressive potential requires knowledge of the mechanism of action. While the cellular mechanisms have been well established, despite numerous efforts the precise molecular mechanism of immunosuppression by cyclosporin A has not been fully elucidated. Our present knowledge is reviewed here. More recently, two further compounds have been introduced as immunosuppressants, FK 506 and rapamycin, of which FK 506 appears to have the same mechanism of action as cyclosporin A, while that of rapamycin is different [4]. Both are discussed in the context of cyclosporin A.