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

• DOI: 10.1007/s00011-008-8007-8
• Publication Date: 2008-11-26T12:13:17Z
• Authors: X. Zhang; Y. Song; X. Ci; N. An; Y. Ju; H. Li; X. Wang; C. Han; J. Cui; X. Deng
• Keywords: Proinflammatory cytokine

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.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.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.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.