Abstract
It has been reported that although the HMG-CoA reductase inhibitor, simvastatin, does not always effectively lower plasma LDL, the drug inhibits LDL oxidation. Simvastatin may therefore prevent atherosclerosis by mechanisms other than its hypocholesterolemic activity. Foam cells in atherosclerotic lesions contain large amounts of cholesterol ester. The direct effects of simvastatin on cholesterol ester accumulation and cytokine production in macrophages have not been described. In this study, we determined whether simvastatin affects cholesterol ester accumulation and cytokine production by THP-1 cells and human peripheral mononuclear cells.
Simvastatin decreased cholesterol ester accumulation without altering phospholipid accumulation in human monocyte THP-1 cells. However, free cholesterol and triglyceride levels rose slightly.
In addition, the production of cytokines was measured in THP-1 cells and human peripheral mononuclear cells stimulated by simvastatin. Simvastatin at doses ranging from 10-9 to 10-5 M did not affect the synthesis of proinflammatory cytokines (IL-1β, IL-6, IL-8 and TNFα) from LPS-PMA-stimulated THP-1 cells. The synthesis of IL-1α, IL-1β, IL-6 and IL-8 from human peripheral mononuclear cells was also unaffected by administration of simvastatin. In addition, any changes in cytokineinduced cytokine production (IL-1-induced IL-8 synthesis) were not detected after the addition of simvastatin. The present results suggest that simvastatin suppresses foam cell formation in monocyte/macrophages, without affecting the immunological or inflammatory function of these cells.
