Inhibitory effects of ivermectin on nitric oxide and prostaglandin E2 production in LPS-stimulated RAW 264.7 macrophages

Int Immunopharmacol. 2009 Mar;9(3):354-9. doi: 10.1016/j.intimp.2008.12.016. Epub 2009 Jan 23.


We have previously shown that ivermectin inhibits LPS-induced production of inflammatory cytokines. In the present study, we investigated the effect of ivermectin on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Ivermectin inhibited LPS-induced NO and PGE(2) production. Consistent with these observations, the protein and mRNA expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes were inhibited by ivermectin in a concentration-dependent manner. Furthermore, the phosphorylation of p38, ERK1/2, and JNK in LPS-stimulated RAW 264.7 cells was suppressed by ivermectin in a dose-dependent manner. These results suggest that ivermectin suppresses NO and PGE(2) production, as well as iNOS and COX-2 expression, by inhibiting phosphorylation of mitogen-activated protein kinases (MAPK) (p38, ERK1/2, and JNK) in LPS-stimulated RAW 264.7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / antagonists & inhibitors*
  • Dinoprostone / biosynthesis
  • Ivermectin / pharmacology*
  • Lipopolysaccharides / immunology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / drug effects
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects


  • Lipopolysaccharides
  • Nitric Oxide
  • Ivermectin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinase Kinases
  • Dinoprostone