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首页> 外文期刊>Infection and immunity >Regulation of serum tumor necrosis factor in glucocorticoid-sensitive and -resistant rodent endotoxin shock models.
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Regulation of serum tumor necrosis factor in glucocorticoid-sensitive and -resistant rodent endotoxin shock models.

机译：在对糖皮质激素敏感和耐药的啮齿动物内毒素休克模型中调节血清肿瘤坏死因子。

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Bolus injection of lethal or sublethal doses of endotoxin or lipopolysaccharide (LPS) results in the rapid and transient rise in tumor necrosis factor (TNF) levels in serum in mammals. TNF levels peak between 1 and 2 h after LPS injection in mice and guinea pigs and approach basal levels by 6 h. Although the kinetics of TNF in serum appear similar between these two species, guinea pigs respond to a lethal dose of LPS of 20 mg/kg by producing approximately 10-fold more TNF than mice do. These two endotoxin shock models also differ in their sensitivity to glucocorticoids. TNF levels in serum are not reduced in the lethal endotoxin shock model in guinea pigs after treatment with dexamethasone at 25 mg/kg. In contrast, TNF levels in mouse serum are inhibited by more than 90% after treatment with dexamethasone at 3 mg/kg. Coincident with the TNF peak in serum is a leukopenia which approaches control levels by 6 h in dexamethasone-treated mice, while remaining depressed in dexamethasone-treated guinea pigs. Treatment with dexamethasone at 25 mg/kg did not save guinea pigs from endotoxin lethality, whereas long-term survival of mice under identical conditions was apparent. These results suggest that the relative glucocorticoid resistance observed in guinea pigs is also apparent in a lethal endotoxin shock model in which dexamethasone does not modulate TNF levels or result in increased survival as occurs in mice. The lack of clear efficacy for steroid therapy in human clinical septic shock trials would suggest that the guinea pig endotoxin model may be a more predictive system than the mouse model for the identification of novel agents useful in the treatment of endotoxin shock.
机译：注射致死剂量或致死剂量的内毒素或脂多糖（LPS）会导致哺乳动物血清中肿瘤坏死因子（TNF）水平迅速而短暂地升高。小鼠和豚鼠注射LPS后1-2小时内TNF水平达到峰值，到6h时接近基础水平。尽管这两个物种之间血清中TNF的动力学相似，但豚鼠对致命剂量的LPS 20 mg / kg的反应是产生的TNF比小鼠高约10倍。这两种内毒素休克模型对糖皮质激素的敏感性也不同。在地塞米松25 mg / kg处理后的豚鼠致死性内毒素休克模型中，血清中的TNF水平并未降低。相反，地塞米松3 mg / kg处理后，小鼠血清中的TNF水平被抑制90％以上。与血清中的TNF峰一致的是白细胞减少症，在地塞米松治疗的小鼠中6小时达到控制水平，而在地塞米松治疗的豚鼠中保持抑郁。地塞米松25 mg / kg的处理不能使豚鼠免受内毒素致死性的影响，而在相同条件下小鼠的长期存活是显而易见的。这些结果表明，在致命的内毒素休克模型中，在地塞米松不调节TNF水平或导致小鼠存活率提高的致命内毒素休克模型中，豚鼠的相对糖皮质激素抵抗也很明显。在人类临床败血症性休克试验中，类固醇疗法缺乏明确的疗效，这表明豚鼠内毒素模型可能比小鼠模型更具预测性，可用于鉴定可用于治疗内毒素休克的新型药物。

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