Insulin Attenuates the Systemic Inflammatory Response to Thermal Trauma

BackgroundInsulin 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 MethodsThermally 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 pro-inflammatory cytokines, anti-inflammatory cytokines, and hepatic signal transcription factor mRNA expression.ResultsInsulin significantly decreased dose dependently serum pro-inflammatory cytokines IL-1β at 1, 5, and 7 days, IL-6 at 1 day, MIF at 5 and 7 days, and TNF at 1 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-β 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).ConclusionsOur 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.