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 (T(H)2 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 T(H)2 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.
Coward
William
W
MRC Toxicology Unit, Hodgkin Building, University of Leicester, PO Box 138, Lancaster Road, Leicester LE1 9HN, UK.
Chow
Sek C
SC
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D011758:Pyrroles / Q000494:pharmacology*; D018417:Th1 Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018418:Th2 Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
D000924:Anticholesteremic Agents; D016207:Cytokines; D006538:Heptanoic Acids; D007166:Immunosuppressive Agents; D011758:Pyrroles; D000069059:Atorvastatin