Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice
X Zhang, Y Song, X Ci, N An, Y Ju, H Li, X Wang, C Han, J Cui, X Deng
Inflammation Research, 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 µg/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-a (TNF-a), 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-a, 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.
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