Statins as immunosuppressive agents - Statins as a newly recognized type of immunomodulator

Background Coronary artery disease in the transplanted heart, also known as cardiac allograft vasculopathy, is one of the major causes of mortality la te after heart transplantation. This accelerated form of atherosclerosis al so affects the donor organs of other transplant recipients including that o f liver, kidney and lung. There are multiple immune and non-immune risk fac tors associated with this disease process, one of which is hyperlipidemia. Use of lipid lowering agents, specifically HMG-CoA reductase inhibitors (st atins) was initially reported to have outcomes benefit and possibly immunos uppressive effects in a single center study of heart transplant recipients. Other subsequent studies have supported this beneficial effect. Method and Results: In a recent paper by Kwak and colleagues, the specific mechanism for this immunosuppressive effect has been elucidated through the use of ex periments monitoring cell surface expression assayed by fluorescence-activa ted cell sorting and by immunofluorescence as well as mRNA levels of major histocompatibility complex class II (MHC-II). They report that statins repr ess induction of MHC-II by interferon-gamma and that this in turn represses activation of T-lymphocytes and other cell types including primary human s mooth. muscle cells and fibroblasts, as well as in established cell. lines such as ThP1, melanomas, and HeLa cells. Conclusion: In addition to previou s clinical and laboratory publications this work by Kwak and colleagues has provided a firm scientific rationale to support the use of statins as adju nct immunosuppressive agents in organ transplantation.