Effects of insulin on hepatic inflammation induced by ethanol and burn injury in a murine model of critical illness.
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.
Emanuele
Mary Ann
MA
Department of Medicine, Division of Endocrinology and Metabolism, Loyola University Medical Center, 2160 South First Avenue, Building 54, Room 137, Maywood, IL 69153, USA.
Emanuele
Nicholas V
NV
Gamelli
Richard L
RL
Kovacs
Elizabeth J
EJ
LaPaglia
Nancy
N
D000818:Animals; D002056:Burns / Q000150:complications*; D015815:Cell Adhesion Molecules; D056486:Chemical and Drug Induced Liver Injury; D016638:Critical Illness; D016207:Cytokines; D000431:Ethanol / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects*; D008107:Liver Diseases / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009504:Neutrophils
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007328:Insulin; D000431:Ethanol