Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hypercholesterolemia

OBJECTIVES The purpose of this study Was to assess if simvastatin has an anti-inflammatory activity in patients with hypercholesterolemia. BACKGROUNDSimvastatin, an inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA) reductase, reduced cardiovascular events in patients with myocardial infarction and hypercholesterolemia. METHODS Sixteen patients with polygenic hypercholesterolemia mere randomly allocated to diet (n = 8) or diet plus 20 mg/day simvastatin (n = 8) for eight weeks. Before and at the end of treatment period, lipid profile and monocyte expression of tumor necrosis factor-alpha (TNF) and interleukin-1 beta (IL-1 beta) were measured. RESULTS At baseline no difference in lipid profile and monocyte expression of TNF and IL-1 beta were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1 beta was seen. In patients with diet plus simvastatin, significant decreases of total cholesterol (-27%, p < 0.02), low density lipoprotein-cholesterol (-33%, p < 0.02), and monocyte expression of TNF (-49%, p < 0.02) and IL-1 beta (-35%, p < 0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1 beta than did patients assigned to diet alone. This study suggests that simvastatin possesses anti-inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL-1 beta expressed by monocytes. (C) 2000 by the American College of Cardiology.