title: Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, 130062, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: X
authors.initials: X
authors.lastname: Ci
authors.forename: N
authors.initials: N
authors.lastname: An
authors.forename: Y
authors.initials: Y
authors.lastname: Ju
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Han
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.forename: X
authors.initials: X
authors.lastname: Deng
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007559:Ivermectin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D007559:Ivermectin