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Immunopathologic Alterations in Murine Models of Sepsis of Increasing Severity

机译：重度脓毒症小鼠模型的免疫病理学改变

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We investigated inflammatory and physiologic parameters in sepsis models of increasing lethality induced by cecal ligation and puncture (CLP). Mice received imipenem for antibiotic therapy, and groups were sacrificed at 2, 4, 8, 12, 16, 20, and 24 h after CLP. The severity of sepsis increased with needle puncture size (lethality with 18-gauge puncture [18G], 100%; 21G, 50%; 25G, 5%; sham treatment, 0%). While the temperature (at 12 h) and the activity and diurnal rhythm (at day 4) of the 25G-treated CLP group recovered to normal, the 21G and 18G treatment groups exhibited severe hypothermia along with decreased activities. A direct correlation was also observed between the severity of sepsis and cytokine (interleukin 1β [IL-1β], tumor necrosis factor [TNF], IL-6, and IL-10) concentrations in both the peritoneum and the plasma. There were substantially higher cytokine levels in the more severe CLP models than in the sham-treated one. Peritoneal and plasma TNF levels were always less than 40 pg/ml in all models. None of the cytokines in the septic mice peaked within the first hour, which is in contrast to the results of most endotoxin models. Chemokine (KC and macrophage inflammatory protein 2) profiles also correlated with the severity of sepsis. Except for the chemokines, levels of inflammatory mediators were always higher at the site of inflammation (peritoneum) than in the circulation. Our study demonstrated that sepsis of increasing severity induced increased cytokine levels both within the local environment (peritoneum) and systemically (plasma), which in turn correlated with morbidity and mortality.
机译：我们调查了盲肠结扎和穿刺（CLP）致死率增加的脓毒症模型中的炎症和生理参数。小鼠接受亚胺培南用于抗生素治疗，CLP后第2、4、8、12、16、20和24小时处死各组。脓毒症的严重程度随穿刺针的大小而增加（18针穿刺的致死率[18G]为100％; 21G为50％; 25G为5％;假手术率为0％）。尽管25G治疗的CLP组的温度（在12 h时）以及活性和昼夜节律（在第4天）恢复到正常，但21G和18G治疗组表现出严重的体温过低，同时活性降低。在腹膜和血浆中脓毒症的严重程度与细胞因子（白介素1β[IL-1β]，肿瘤坏死因子[TNF]，IL-6和IL-10）的浓度之间也存在直接相关性。在较严重的CLP模型中，其细胞因子水平明显高于假治疗的模型。在所有模型中，腹膜和血浆TNF水平始终低于40 pg / ml。与大多数内毒素模型的结果相反，败血症小鼠中的细胞因子在第一个小时内均未达到峰值。趋化因子（KC和巨噬细胞炎性蛋白2）谱也与败血症的严重程度相关。除了趋化因子外，炎症部位（腹膜）的炎症介质水平始终高于循环系统。我们的研究表明，脓毒症的严重程度不断提高，导致局部环境（腹膜）和全身（血浆）内的细胞因子水平升高，这又与发病率和死亡率相关。

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