Simvastatin Inhibits the Monocyte Expression of Proinflammatory Cytokines in Patients With Hypercholesterolemia

J Am Coll Cardiol. 2000 Aug;36(2):427-31. doi: 10.1016/s0735-1097(00)00771-3.

Abstract

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-alpha (TNF) and interleukin-1beta (IL-1beta) were measured.

Results: At baseline no difference in lipid profile and monocyte expression of TNF and IL-1beta were observed between the two groups. In patients allocated to diet alone, no change in lipid profile and monocyte expression of TNF and IL-1beta 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-1beta (-35%, p<0.02) were observed. At the end of treatment period, patients treated with simvastatin had lower cholesterol and monocyte TNF and IL-1beta 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-1beta expressed by monocytes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Anti-Inflammatory Agents / pharmacology*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / drug therapy*
  • Interleukin-1 / metabolism*
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • Simvastatin / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Simvastatin