Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice
Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice
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DOI：
10.1007/s00011-008-8007-8
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发表时间：
2008-11-01
影响因子：
6.7
通讯作者：
Deng, X.
中科院分区：
文献类型：
--
作者：
Zhang, X.;Song, Y.;Deng, X.
为了研究大环内酯家族的半合成衍生物伊维菌素是否能够在体内和体外抑制脂多糖（LPS）诱导的炎症。C57BL/6小鼠口服伊维菌素（或生理盐水），并以致死剂量32 mg/kg腹膜内注射LPS。用 1 μg/ml LPS（加或不加伊维菌素）刺激 RAW 264.7 鼠巨噬细胞 6、12 和 24 小时。通过 ELISA 测量小鼠血清和细胞上清液中肿瘤坏死因子-α (TNF-α)、白细胞介素 1A (IL-1A) 和白细胞介素 6 (IL-6) 的产生。通过免疫细胞化学分析评估核因子-kB (NF-kB) 与 p65 亚基的易位。伊维菌素可提高致死剂量 LPS 诱导的小鼠存活率。此外，伊维菌素在体内和体外显着降低TNF-α、IL-1A和IL-6的产生。此外，伊维菌素还能抑制LPS诱导的NF-kB易位。结果表明，伊维菌素可能通过阻断NF-kB通路来抑制LPS诱导的炎症细胞因子的产生，提高LPS诱导的小鼠存活率。这一发现可能为治疗内毒素血症和相关炎症提供新策略。
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 mu g/ml, with or without ivermectin for 6, 12 and 24 h. The production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1A (IL-1A) 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-1A 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.