Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice.
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.
Zhang
X
X
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, 130062, China.
Song
Y
Y
Ci
X
X
An
N
N
Ju
Y
Y
Li
H
H
Wang
X
X
Han
C
C
Cui
J
J
Deng
X
X
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
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D007559:Ivermectin