In Vitro Studies of the Immunomodulatory Effects of Statins Alone and in Combination with Immunosuppressive Drugs

Abstract

The effects of statins go beyond their lipid-lowering properties and include immunomodulatory and anti-inflammatory effects. Unfortunately, there is a lack of in vitro assays that study the immunomodulatory effect of statins at therapeutic concentrations and the possible synergism with immunosuppressive drugs. Besides, they are mostly evaluated on isolated peripheral blood mononuclear cells instead of using whole blood as a matrix. The aim of this study is to perform in vitro experiments to evaluate the effect of atorvastatin, simvastatin and fluvastatin at therapeutic concentrations alone and in combination with everolimus or tacrolimus on immunosuppressive response, using whole blood as a matrix by investigating lymphocyte proliferation and production of the soluble cytokines interleukin (IL)-2, IL-10 and interferon (IFN)-γ. Statins (0.1 μM) inhibited T cell proliferation by 12–16% in a dose-dependent manner and when statins at 0.1 μM were combined with each immunosuppressive drug at 8 ng/ml, inhibition increased by 6–9% (p<0.05) for everolimus and 8–15% (p<0.05) for tacrolimus, but not for atorvastatin. At a dose of 0.1 μM, all three statins inhibited soluble IFN-γ production by approximately 5–9% (p<0.02). IL-2 and IL-10 production were unaltered by the presence of statins. These findings suggest that statins seem to exert a mild anti-inflammatory effect that might potentially be used to treat autoimmune diseases.