Dual roles of HMG-CoA reductase inhibitors in solid organ transplantation: lipid lowering and immunosuppression.

Hyperlipidemia has been associated with the development of transplant coronary vasculopathy (TCV) in heart transplant recipients and chronic rejection in kidney transplant recipients. HMG-CoA reductase inhibitors (HMGCoARIs) are effective in treating post-transplant hyperlipidemia, but their effects on patient and graft outcome remain unclear. In a prospective randomized trial investigating pravastatin (PVS) use early after heart transplantation, we observed that PVS treated patients had a decreased incidence of clinically severe acute rejection episodes resulting in a significant improvement in one year survival (94% vs. 78% in the control group, P = 0.02), and decreases in both the incidence and progression of TCV. This observation was validated in a prospective randomized study of kidney transplant recipients where we found that PVS reduced the incidence of acute rejection episodes (25% vs. 58% in the control group, P = 0.01). In both the heart and kidney transplant recipients, taking PVS, we noted decreases in natural killer cell (NKC) cytotoxicity. In vitro studies reveal that: PVS inhibits NKC cytotoxicity; PVS acts synergistically with cyclosporine to inhibit cytotoxic lymphocyte activity; and, other HMGCoARIs inhibit T-cell proliferation and monocyte chemotaxis. In conclusion, HMGCoARIs may have immunosuppressive properties in transplant recipients that could be useful in combating acute and chronic rejection.