Everolimus and Sirolimus antagonize Tacrolimus based calcineurin inhibition via competition for FK-binding protein 12

Huub H. van Rossum , Fred P.H.T.M. Romijn , Nico P.M. Smit , Johan W. de Fijter , Johannes van Pelt

The calcineurin inhibitors cyclosporin A and tacrolimus and the inhibitors of the mTOR, sirolimus and everolimus bind immunophilins that are required for their immunosuppressive action. In contrast to cyclosporin A, tacrolimus and the mTOR inhibitors (MTIs) share common immunophilins, the FK506-binding proteins (FKBPs). We investigated the immunosuppressive interactions of MTIs on tacrolimus based immune suppression, since insights in immunological drug-drug interactions can be very relevant for optimization of immunosuppressive regimens in allograft transplantation medicine.

Mots clés: PHA; PMA; RPMI; iFCS; IC; CI; IL; SEM; Calcineurin; tacrolimus; everolimus; sirolimus; transplantation; CN; TRL; mTOR; MTIs; FKBP; PBMCs; CsA; SRL; EVL

Huub H. van Rossum, Fred P.H.T.M. Romijn, Nico P.M. Smit, Johan W. de Fijter, Johannes van Pelt. Everolimus and Sirolimus antagonize Tacrolimus based calcineurin inhibition via competition for FK-binding protein 12. Biochemical Pharmacology, 2009, 77 (7), pp.1206. ⟨10.1016/j.bcp.2008.12.009⟩. ⟨hal-00493479⟩