Atorvastatin down-regulates the primate cellular response to porcine aortic endothelial cells in vitro.

Using mixed lymphocyte reaction (MLR), the effect of atorvastatin on proliferation of human and baboon peripheral blood mononuclear cells (PBMCs) and human CD4+ T cells in response to wild-type (WT) and alpha-1,3-galactosyltransferase gene-knockout (GTKO) porcine aortic endothelial cells (pAECs) was investigated. swine leukocyte antigen class-II (SLA II) expression on pAEC before and after porcine interferon gamma (pIFN-gamma) stimulation, and the effect of atorvastatin on this expression was assessed. Added to the MLR, atorvastatin reduced (i) the human PBMC response to unstimulated (P<0.05) and (ii) the human and baboon PBMC responses to stimulated (P<0.05) WT and GTKO pAEC. Atorvastatin treatment of human PBMC before MLR reduced their response to stimulated WT (P<0.05) and GTKO (P<0.05) pAEC. Stimulation of pAEC with pIFN-gamma increased SLA II expression 20- to 60-fold, which was down-regulated by atorvastatin. Atorvastatin treatment of stimulated pAEC before MLR reduced proliferation of human PBMC (P<0.05) and CD4+ T cells (P<0.05). Atorvastatin down-regulates the primate cellular xenoresponse, possibly through its antiproliferative effect on PBMCs and the reduction of SLA II on pAECs.