Cyclosporine-Induced Autoimmunity and Immune Hyperreactivity

Abstract

Cyclosporine (cyclosporin A) is a potent immunosuppressive agent which has been extensively used clinically to treat or prevent allograft rejection, graft-vs-host-disease (GVHD), and autoimmune diseases¹. In this review, we analyze various experimental and clinical situations where paradoxically cyclosporine (CS) has been shown to either enhance delayed-type hypersensitivity (DTH), enhance alloreactive responses, aggravate autoimmune diseases, or to actually induce specific forms of autoimmunity. The diverse paradoxical effects of this immunosuppressive agent are probably not due to a single mechanism, but rather reflect the ability of CS to cripple various immunoregulatory and tolerance mechanisms. Before discussing the paradoxical effects of cyclosporine, we will briefly review current knowledge of the mode of action of this drug.

Key Words:

• Autoimmunity
• cyclosporine
• syngeneic graft-vs-host disease
• thymus
• tolerance