Statins as immunomodulatory agents.
Statins have long been thought to exert their benefits by reducing cholesterol synthesis. However, the fact that mevalonate is the precursor of isoprenoids that regulate diverse cellular functions has led investigators to examine pleiotropic effects for these agents. Major histocompatibility complex class II (MHC-II) molecules, which affect the immune response and organ rejection after transplantation, may be induced by the proinflammatory cytokine interferon gamma (IFN-gamma). An experiment was conducted to determine whether statins affect the regulation of MHC-II expression by IFN-gamma in cultured human endothelial cells and monocyte/macrophages. Statins were found to repress the induction of MHC-II by IFN-gamma. This may explain the immunosuppressive effects of statins seen in two clinical trials of organ transplantation and suggest a potential role for statins as immunosuppressive agents.
Mach
François
F
Cardiology Division, Department of Medicine, University Hospital, Geneva Medical School, Foundation for Medical Research, Geneva, Switzerland. francois.mach@medicine.unige.ch
D000069059:Atorvastatin; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006538:Heptanoic Acids / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation; D011758:Pyrroles / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D006538:Heptanoic Acids; D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D011758:Pyrroles; D007371:Interferon-gamma; D000069059:Atorvastatin