Emanuele Mary Ann, Emanuele Nicholas V, Gamelli Richard L, Kovacs Elizabeth J, LaPaglia Nancy
Department of Medicine, Division of Endocrinology and Metabolism, Loyola University Medical Center, 2160 South First Avenue, Building 54, Room 137, Maywood, IL 69153, USA.
J Burn Care Res. 2007 May-Jun;28(3):490-9. doi: 10.1097/BCR.0B013E318053DAED.
In recent, landmark clinical trials, insulin to maintain euglycemia in critically ill patients improved clinical outcomes, including decreased all-cause mortality. Novel antiinflammatory effects of insulin have recently been described. Thermal injury is an excellent model of critical illness. The addition of ethanol to the model is of great clinical relevance because nearly 50% of the patients admitted to hospitals for burn injuries have ethanol in their circulation. Utilizing a murine model of critical illness (ethanol and skin burn), we tested the hypothesis that insulin treatment in ethanol-exposed, burn-injured mice reduced hepatic inflammation, a potential mechanism for the benefit of insulin. Adult male C57BL/6 mice were given a single intraperitoneal injection of ethanol or saline, were given a 15% total body full-thickness skin burn, or were sham-burned and killed 24 hours later. In each group, half the animals were given subcutaneous injections of the long-lasting basal insulin glargine; the other half, the appropriate vehicle. Hepatic inflammatory markers, including polymorphonuclear infiltration, a chemokine, an important adhesion molecule, proinflammatory cytokines, and nuclear factor kappaB, were measured, and all were increased by ethanol and/or burn. These increases were prevented by insulin. An antiinflammatory cytokine was reduced by ethanol and/or burn. Insulin prevented this decrease. Thus, insulin has a substantial antiinflammatory effect, and this may underlie its dramatic clinical benefit in critical illness.
在最近具有里程碑意义的临床试验中，在重症患者中使用胰岛素维持血糖正常改善了临床结局，包括降低全因死亡率。最近还描述了胰岛素的新型抗炎作用。热损伤是危重病的一个理想模型。在该模型中加入乙醇具有重要的临床意义，因为因烧伤入院的患者中近50%的血液循环中有乙醇。利用一种危重病小鼠模型（乙醇和皮肤烧伤），我们检验了以下假设：在暴露于乙醇、有烧伤的小鼠中进行胰岛素治疗可减轻肝脏炎症，这是胰岛素发挥有益作用的一种潜在机制。成年雄性C57BL/6小鼠单次腹腔注射乙醇或生理盐水，给予15%的全身全层皮肤烧伤，或进行假烧伤，24小时后处死。在每组中，一半动物皮下注射长效基础胰岛素甘精胰岛素；另一半注射相应的溶媒。检测了肝脏炎症标志物，包括多形核白细胞浸润、一种趋化因子、一种重要的黏附分子、促炎细胞因子和核因子κB，所有这些标志物均因乙醇和/或烧伤而增加。胰岛素可防止这些增加。一种抗炎细胞因子因乙醇和/或烧伤而减少。胰岛素可防止这种减少。因此，胰岛素具有显著的抗炎作用，这可能是其在危重病中产生显著临床益处的基础。
