Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice

Inflamm Res. 2008 Nov;57(11):524-9. doi: 10.1007/s00011-008-8007-8.


Objective and design: To investigate whether ivermectin, a semi-synthetic derivative of a family of macrocyclic lactones could inhibit lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro.

Materials and methods: C57BL/6 mice were administered ivermectin (or saline) orally and challenged intraperitoneally with LPS at a lethal dose of 32 mg/kg. RAW 264.7 murine macrophages were stimulated with LPS at 1 microg/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1ss (IL-1ss) and interleukin-6 (IL-6) in serum from mice and supernatants from cells were measured by ELISA. Nuclear factor-kB (NF-kB) translocation with subunit p65 was evaluated by immunocytochemical analysis.

Results: Ivermectin improved mouse survival rate induced by a lethal dose of LPS. In addition, ivermectin significantly decreased the production of TNF-alpha, IL-1ss and IL-6 in vivo and in vitro. Furthermore, ivermectin suppressed NF-kB translocation induced by LPS.

Conclusions: The results indicate that ivermectin may inhibit LPS-induced production of inflammatory cytokines by blocking NF-kB pathway and improve LPS-induced survival in mice. This finding might provide a new strategy for the treatment of endotoxemia and associated inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / biosynthesis*
  • Female
  • Ivermectin / pharmacology*
  • Lipopolysaccharides / antagonists & inhibitors*
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Protein Transport / drug effects


  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Ivermectin