Authors: Zhang X, Song Y, Ci X, An N, Ju Y

PMID: 19109745 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.

Keywords: ivermectin, inflammatory cytokines, LPS

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