Ezetimibe and atorvastatin both immunoregulate CD4+T cells from cardiac transplant recipients in vitro

Background: Statins are LDL lowering agents that reduce cardiac allograft vasculopathy (CAV) incidence after cardiac transplantation. Furthermore, 'pleiotropic effects' including immunomodulation have been demonstrated by statins following transplantation. It has also been previously suggested that ezetimibe may exert specific effects on the innate immune system in vitro. We compared the effects of ezetimibe and atorvastatin on T lymphocytes in vitro on the justification that these cells are implicated in the pathogenesis of atherosclerosis, allograft rejection and CAV. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 30 cardiac transplant recipients and co-cultured with the study drug (or placebo) over 48 h. In total, 150 cultures were performed (5 per patient). Drug concentrations were calculated to simulate 10 mg or 100 mg daily in a 70 kg adult. Flow cytometry was performed to analyse T lymphocyte counts and functional characteristics. Results: Ezetimibe reduced the standard CD3+CD4+ T cell count and CD3+CD4+CD45ro T memory count by dose linear effect (p<0.001). Atorvastatin also reduced the CD3+CD4+ T cell count and CD3+CD4+CD45ro T memory count by dose linear effect (p=0.005). Neither drug affected CD3+CD8+ cytotoxic T cells. Discussion: Both atorvastatin and ezetimibe may have selective immunomodulatory properties independent of their mechanisms of LDL lowering, given that both drugs affect CD4 T helper cells but have no effect on CD8 cytotoxic lymphocytes in vitro. Although speculative, both of these agents could potentially offer benefits to the transplant patient by modulating important components of the adaptive immune system. CD4+ cells in particular are implicated in both CAV and rejection processes. (C) 2009 Elsevier B.V. All rights reserved.