Inhibition of monocyte chemotactic protein-1 synthesis by statins

Lab Invest. 2000 Jul;80(7):1095-100. doi: 10.1038/labinvest.3780115.


The beneficial effects of statins on the reduction of cardiovascular events has been partly attributed to their anti-inflammatory properties. In the complex of the different pathogenetic events leading to atherosclerosis, recent data suggest a central role of monocyte chemotactic protein-1 (MCP-1), because mice knock-out for MCP-1 or its receptor CC-chemokine receptor 2 were considerably resistant to plaque formation. In this study we investigated the effect of different statins on in vitro and in vivo production of MCP-1. Lovastatin and simvastatin caused a dose-dependent inhibition of MCP-1 production in peripheral blood mononuclear cells exposed to lipopolysaccharide or inactivated Streptococcus hemoliticus and in human endothelial cells exposed to interleukin-1beta. The addition of mevalonate overrode the inhibitory effect of statins indicating that mevalonate-derived products are important for chemokine production. The in vivo anti-inflammatory effect of statins was investigated using the mouse air-pouch model of local inflammation. Lovastatin and pravastatin were orally administered to mice according to a treatment schedule that significantly inhibited the hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity without affecting total blood cholesterol. At the dose of 10 mg/kg, lovastatin and pravastatin reduced by approximately 50% the lipopolysaccharide-induced leukocytes recruitment and the exudate MCP-1 production. In conclusion, statins, by inhibiting mevalonate-derived products, reduced both in vitro and in vivo the production of chemokines involved in leukocyte migration, and this effect is unrelated to their cholesterol-lowering action.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / blood
  • Chemokine CCL2 / genetics
  • Dose-Response Relationship, Drug
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Leukocytes / physiology
  • Lovastatin / pharmacology*
  • Mevalonic Acid / antagonists & inhibitors
  • Monocytes / metabolism
  • Pravastatin / pharmacology*
  • RNA, Messenger / blood
  • Simvastatin / pharmacology*


  • Chemokine CCL2
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RNA, Messenger
  • Lovastatin
  • Simvastatin
  • Pravastatin
  • Mevalonic Acid