What is the mechanism of action of cyclosporine and tacrolimus?
Cyclosporine and tacrolimus are both calcineurin inhibitors. They first bind to, respectively, cyclophilin or FKBP (FK binding-protein). This drug/protein complex then binds to and inhibits the activity of calcineurin. Calcineurin dephosphorylates a transcription factor called nuclear factor of activated T-cells (NFAT). This prevents NFAT from entering the nucleus and promoting transcription of several cytokines. The most important of these cytokines is IL-2, while others include IL-4, IFN-g and TNF-a. Inhibition of IL-2 and other cytokines leads to downregulation of T cell responses.