Clinical and mechanistic differences between FK506 (tacrolimus) and cyclosporin A

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Abstract
Cyclosporin A (CsA) and FK506 (tacrolimus) are potent immunosuppressive drugs widely used in reducing the incidence and severity of allograft rejection after organ transplantation. Owing to their capacity to antagonize calcineurin activity and hence calcium‐dependent T‐cell activation [1], both drugs were thought to have identical cellular and molecular effects, despite differences in their structure [2]. This notion was challenged by both clinical and experimental evidence clearly showing that CsA and FK506 immunosuppressive effects are not identical, and that FK506 affects CsA‐sensitive and CsA‐insensitive T‐cell activation pathways. Here we discuss recent findings, including our own, which highlight differences in efficacy and mechanisms between CsA and FK506.