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

OBJECTIVE The purpose of this study was to assess if simvastatin has an anti-inflammatory activity in patients with hypercholesterolemia. BACKGROUND Simvastatin, 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 were 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-α (TNF) and interleukin-1β (IL-1β) were measured. RESULTS At baseline no difference in lipid profile and monocyte expression of TNF and IL-1β were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1β 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-1β (−35%, p < 0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1β than did patients assigned to diet alone. CONCLUSION This study suggests that simvastatin possesses anti-inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL-1β expressed by monocytes.