Molecular actions of calcineurin inhibitors

The immunosuppressive drugs cyclosporin A and FK-506, also called calcineurin inhibitors, have been useful for treating immune system-mediated diseases and have truly revolutionized allograft transplantation. Both drugs block T-cell proliferation by mechanisms that involve the inhibition of the key signaling phosphatase calcineurin, hence, the name calcineurin inhibitors. The inhibition of calcineurin activation by cyclosporin A and FK-506 blocks T-cell receptor-mediated production of interleukin-2 (IL-2), a growth factor critical for T-cell proliferation. Recent studies, however, suggest that the effects of the drugs are not limited to blocking calcineurin activation and IL-2 production. This review discusses the molecular actions of cyclosporin A and FK-506.