Insulin attenuates the systemic inflammatory response to thermal trauma
Insulin attenuates the systemic inflammatory response to thermal trauma
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DOI：
10.1007/bf03402024
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发表时间：
2002-08-01
影响因子：
5.7
通讯作者：
Jauch, KW
中科院分区：
文献类型：
--
作者：
Jeschke, MG;Einspanier, R;Jauch, KW
背景：最近已证明胰岛素可以降低危重患者的死亡率并预防多器官衰竭的发生。胰岛素改善生存的分子机制尚未明确。本研究的目的是确定胰岛素治疗对全身炎症反应的影响。在体内，我们确定了胰岛素治疗对热损伤诱导的炎症级联的影响。 材料和方法：热损伤大鼠 (30% TBSA) 被随机分为两组，接受生理盐水 (n = 28) 或胰岛素 (n = 28)。我们的结果测量包括胰岛素对促炎细胞因子、抗炎细胞因子和肝信号转录因子 mRNA 表达的影响。结果：与对照组相比，胰岛素以剂量依赖性方式显着降低损伤后第 1 天、第 5 天和第 7 天的血清促炎细胞因子 IL-1beta、第 1 天的 IL-6、第 5 天和第 7 天的 MIF、以及第 1 天和第 2 天的 TNF（p < 0.05）。与对照组相比，胰岛素在创伤后 5 天和 7 天增加了抗炎细胞因子 IL-2 和 IL-4，在创伤后 2、5 和 7 天增加了 IL-10（p < 0.05）。促炎信号转录因子 STAT-5 和 C/EBP-β mRNA 在创伤后 1 天和 2 天显着减少；损伤后 7 天，胰岛素增加了 SOCS-3 和 RANTES 的抗炎信号转录因子 mRNA 表达（p < 0.05）。结论：我们的数据表明，胰岛素通过减少促炎和增加抗炎级联来减弱炎症反应，从而恢复全身稳态，这已被证明对危重患者的器官功能和生存至关重要。
Background: Insulin has been recently shown to decrease mortality and prevent the incidence of multi-organ failure in critically ill patients. The molecular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin therapy on the systemic inflammatory response. In vivo we determined the effect of insulin therapy on the inflammatory cascade, which was induced by thermal injury.Materials and Methods: Thermally injured rats (30% TBSA) were randomly divided into two groups to receive either saline (n = 28) or insulin (n = 28). Our outcome measures encompassed the effect of insulin on proinflammatory cytokines, anti-inflammatory cytokines, and hepatic signal transcription factor mRNA expression.Results: insulin significantly decreased dose dependently serum pro-inflammatory cytokines IL-1beta at 1, 5, and 7 days, IL-6 at 1 day, MIF at 5 and 7 days, and TNF at I and 2 days after injury when compared with controls (p < 0.05). Insulin increased anti-inflammatory cytokines IL-2 and IL-4 at 5 and 7 days after trauma, and IL-10 at 2, 5 and 7 days after trauma when compared with controls (p < 0.05). Pro-inflammatory signal transcription factors STAT-5 and C/EBP-beta mRNA were significantly decreased 1 and 2 days posttrauma; insulin increased anti-inflammatory signal transcription factor mRNA expression of SOCS-3 and RANTES 7 days after the injury (p < 0.05).Conclusions: Our data provide insight that insulin attenuates the inflammatory response by decreasing the proinflammatory and increasing the anti-inflammatory cascade, thereby restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.