X Zhang1, Y Song, X Ci, N An, Y Ju, H Li, X Wang, C Han, J Cui, X Deng. 1. Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, 130062, China.
Abstract
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.
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.
Authors: A Nihal Sari; Belma Korkmaz; Mehmet Sami Serin; Meltem Kacan; Demet Unsal; C Kemal Buharalioglu; Seyhan Sahan Firat; Vijay L Manthati; John R Falck; Kafait U Malik; Bahar Tunctan Journal: Inflamm Res Date: 2014-06-12 Impact factor: 4.575
Authors: Ankit Shah; Ashish S Verma; Kalpeshkumar H Patel; Richard Noel; Vanessa Rivera-Amill; Peter S Silverstein; Suman Chaudhary; Hari K Bhat; Leonidas Stamatatos; Dhirendra P Singh; Shilpa Buch; Anil Kumar Journal: PLoS One Date: 2011-06-21 Impact factor: 3.240