Simvastatin decreases IL-6 and IL-8 production in epithelial cells

J Dent Res. 2006 Jun;85(6):520-3. doi: 10.1177/154405910608500608.


Many cardiovascular studies have suggested that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors (statins) have anti-inflammatory effects independent of cholesterol lowering. As a chronic inflammatory disease, periodontitis shares some mechanisms with atherosclerosis. Since oral epithelial cells participate importantly in periodontal inflammation, we measured simvastatin effects on interleukin-6 and interleukin-8 production by cultured human epithelial cell line (KB cells) in response to interleukin-1alpha. Simvastatin decreased production, an effect reversed by adding mevalonate or geranylgeranyl pyrophosphate, but not farnesyl pyrophosphate. Simvastatin was found to reduce NF-kappaB and AP-1 promoter activity in KB cells. Dominant-negative Rac1 severely inhibited interleukin-1alpha-induced NF-kappaB and AP-1 promoter activity. Our results may indicate an anti-inflammatory effect of simvastatin on human oral epithelial cells, apparently involving Rac1 GTPase inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Epithelial Cells / drug effects
  • Gingiva / cytology
  • Gingiva / drug effects*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hypolipidemic Agents / pharmacology*
  • Interleukin-1 / pharmacology
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-8 / antagonists & inhibitors*
  • KB Cells
  • Mevalonic Acid / pharmacology
  • NF-kappa B / drug effects
  • Polyisoprenyl Phosphates / pharmacology
  • Sesquiterpenes
  • Simvastatin / pharmacology*
  • Transcription Factor AP-1 / drug effects
  • rho GTP-Binding Proteins / antagonists & inhibitors
  • rho GTP-Binding Proteins / pharmacology


  • Anti-Inflammatory Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Interleukin-1
  • Interleukin-6
  • Interleukin-8
  • NF-kappa B
  • Polyisoprenyl Phosphates
  • Sesquiterpenes
  • Transcription Factor AP-1
  • farnesyl pyrophosphate
  • Simvastatin
  • rho GTP-Binding Proteins
  • geranylgeranyl pyrophosphate
  • Mevalonic Acid