Zhang X, Song Y, Ci X, An N, Ju Y, Li H, Wang X, Han C, Cui J, Deng X
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, 130062, China.
Inflamm Res. 2008 Nov;57(11):524-9. doi: 10.1007/s00011-008-8007-8.
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.
研究大环内酯类半合成衍生物伊维菌素在体内和体外是否能抑制脂多糖（LPS）诱导的炎症反应。
给C57BL/6小鼠口服伊维菌素（或生理盐水），然后腹腔注射致死剂量为32 mg/kg的LPS。用1 μg/ml的LPS刺激RAW 264.7小鼠巨噬细胞，分别在有或无伊维菌素的情况下培养6、12和24小时。通过酶联免疫吸附测定法（ELISA）检测小鼠血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的生成，以及细胞培养上清液中这些细胞因子的生成。通过免疫细胞化学分析评估核因子-κB（NF-κB）亚基p65的易位情况。
伊维菌素提高了致死剂量LPS诱导的小鼠存活率。此外，伊维菌素在体内和体外均显著降低了TNF-α、IL-1β和IL-6的生成。而且，伊维菌素抑制了LPS诱导的NF-κB易位。
结果表明，伊维菌素可能通过阻断NF-κB途径抑制LPS诱导的炎性细胞因子生成，并提高LPS诱导的小鼠存活率。这一发现可能为内毒素血症及相关炎症的治疗提供新策略。
