Effect of atorvastatin on TH1 and TH2 cytokine secreting cells during T cell activation and differentiation

Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are the most effective agents for the lowering of cholesterol in clinical practice. In addition to their lipid-lowering properties, statins also have immunomodulatory activities. Animal studies have shown that statins promote a T helper 2 (T(H)2) bias and suppress the secretion of T helper 1 (T(H)1) cytokines. We therefore examine whether atorvastatin modulates the T(H)1/T(H)2 responses in human T cells. Using primary T cells as well as differentiated T(H)1 and T(H)2 cells, the immunomodulatory effect of atorvastatin on cells secreting IFN-gamma (T(H)1 response) and IL-4 (TH2 response) was investigated. Atorvastatin had no effect on cells secreting IFN-gamma and IL-4 in primary T cells stimulated with anti-CD3 and -CD28 antibodies. Similarly, cells producing IFN-gamma and IL-4 in stable differentiated T(H)1 and T(H)2 cells were unaffected by atorvastatin. Furthermore, atorvastatin had no effect on the ratio of IFN-gamma(+)/IL-4(+) cells during the differentiation of T(H)0 cells to T(H)1 and TH2 cells in long-term cultures. These data suggest that atorvastatin does not have any immunomodulatory effect on the T(H)1/T(H)2 balance in human T cells in vitro. (c) 2005 Elsevier Ireland Ltd. All rights reserved.