Effects of an HMG-CoA reductase inhibitor on cytokine production by human monocytes/macrophages.

It has been reported that the HMG-CoA reductase inhibitor simvastatin does not always effectively lower plasma LDL. This drug acts to monocytes/macrophages directly and inhibits cholesterol ester accumulation in these cells. However cytokine production in macrophages when simvastatin was administrated has not been described. In this study, we examined whether simvastatin affects cytokine production in human monocyte-derived macrophages. Simvastatin at doses ranging from 10(-9) to 10(-5) M did not affect the synthesis of proinflammatory cytokines (IL-1 beta, IL-6, IL-8) from human peripheral mononuclear cells. In addition, any changes in cytokine-induced 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/macrophage, without affecting the immunological or inflammatory functions of these cells.