Statins as immunosuppressive agents.
BACKGROUND
Coronary artery disease in the transplanted heart, also known as cardiac allograft vasculopathy, is one of the major causes of mortality late after heart transplantation. This accelerated form of atherosclerosis also affects the donor organs of other transplant recipients including that of liver, kidney and lung. There are multiple immune and non-immune risk factors associated with this disease process, one of which is hyperlipidemia. Use of lipid lowering agents, specifically HMG-CoA reductase inhibitors (statins) was initially reported to have outcomes benefit and possibly immunosuppressive effects in a single center study of heart transplant recipients. Other subsequent studies have supported this beneficial effect.


RESULTS
In a recent paper by Kwak and colleagues, the specific mechanism for this immunosuppressive effect has been elucidated through the use of experiments monitoring cell surface expression assayed by fluorescence-activated cell sorting and by immunofluorescence as well as mRNA levels of major histocompatibility complex class II (MHC-II). They report that statins repress induction of MHC-II by interferon-gamma and that this in turn represses activation of T-lymphocytes and other cell types including primary human smooth muscle cells and fibroblasts, as well as in established cell lines such as ThP1, melanomas, and HeLa cells.


CONCLUSIONS
In addition to previous clinical and laboratory publications this work by Kwak and colleagues has provided a firm scientific rationale to support the use of statins as adjunct immunosuppressive agents in organ transplantation.
Kobashigawa
J A
JA
Division of Cardiology University of California at Los Angeles Medical Center 100 UCLA Medical Plaza, #630 Los Angeles, CA 90095.
D000818:Animals; D003327:Coronary Disease / Q000517:prevention & control; D000949:Histocompatibility Antigens Class II; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D014181:Transplantation Immunology
D000949:Histocompatibility Antigens Class II; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D007166:Immunosuppressive Agents