High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis
High-dose intravenous immunoglobulin G improves systemic inflammation in a rat model of CLP-induced sepsis
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DOI：
10.1007/s00134-008-1161-1
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发表时间：
2008-10-01
影响因子：
38.9
通讯作者：
Noguchi, Takayuki
中科院分区：
文献类型：
--
作者：
Hagiwara, Satoshi;Iwasaka, Hideo;Noguchi, Takayuki
目的：静脉注射免疫球蛋白治疗已被提议作为脓毒症的先进治疗方法。然而，其益处仍不清楚，其作用机制也知之甚少。脓毒症发生过程中的一个关键介质是高迁移率族蛋白 1 (HMGB1)。因此，我们检测了脓毒症大鼠模型中 HMGB1 的血清和肺组织水平。设计和设置：在大学实验室进行前瞻性对照动物研究。材料：大鼠接受盲肠结扎和穿刺引起的脓毒症，或接受额外的静脉注射免疫球蛋白治疗，推注剂量为 100、300 或 1,000 mg/kg。测量和结果：诱导败血症和相应的治疗条件后，检查肺组织中的组织病理学、湿/干重量比和信号分子。测量细胞因子和 HMGB1 的血清和肺部水平。与对照大鼠相比，高剂量静脉注射免疫球蛋白（1,000 mg/kg）治疗的动物表现出显着改善的存活率和肺组织病理学。在静脉注射免疫球蛋白治疗的动物中，血清和肺部 HMGB1 水平随着时间的推移而降低。此外，静脉注射免疫球蛋白可抑制 NF-κ B 活性。结论：高剂量静脉注射免疫球蛋白可降低脓毒症大鼠模型的死亡率和肺部病理学。还观察到 HMGB1 水平显着降低，这可能是通过抑制炎症和 NF-κ B 介导的。 描述：23. 急性呼吸窘迫综合征 (ARDS) 和急性肺损伤 (ALI)：实验模型。
Objective: Intravenous immunoglobulin therapy has been proposed as an advanced treatment for sepsis. Yet, its benefit remains unclear and the mechanism of action is poorly understood. One key mediator in the development of sepsis is high mobility group box 1 (HMGB1). Therefore, we examined the serum and lung tissue levels of HMGB1 in a rat model of sepsis. Design and setting: Prospective controlled animal study in a university laboratory. Materials: Rats received either cecal ligation and puncture-induced sepsis or had additional intravenous immunoglobulin treatment in boluses of 100, 300, or 1,000 mg/kg. Measurements and results: After induction of sepsis and respective treatment conditions, histopathology, wet/dry weight ratios, and signaling molecules were examined in pulmonary tissue. Serum and pulmonary levels of cytokine and HMGB1 were measured. High dose intravenous immunoglobulin (1,000 mg/kg)-treated animals demonstrated significantly improved survival and pulmonary histopathology compared to the control rats. Serum and pulmonary HMGB1 levels were lower over time among intravenous immunoglobulin-treated animals. Furthermore, administration of intravenous immunoglobulin resulted in inhibition of NF-kappa B activity. Conclusions: High-dose intravenous immunoglobulin decreased the mortality and pulmonary pathology in a rat model of sepsis. A significant reduction in HMGB1 levels was also observed, which may be mediated by inhibition of inflammation and NF-kappa B. Descriptor: 23. Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI): experimental models.