Insulin Treatment Improves the Systemic Inflammatory Reaction to Severe Trauma

In Brief Objective: Determine the effect of insulin on the systemic inflammatory response, pro- and anti-inflammatory cytokines and hepatic acute-phase-response in severely burned pediatric patients. Summary Background Data: The systemic inflammatory and hepatic acute-phase-response contribute to hypermetabolism, multi-organ failure, and mortality. Insulin has been recently shown to decrease mortality and to prevent the incidence of multi-organ failure in critically ill patients; however, the underlying mechanisms have not been defined. Methods: Thirteen thermally injured children received insulin to maintain blood glucose at a range from 120 to 180 mg/dl, 15 children received no insulin with blood glucose levels also at range from 120 to 180 mg/dl and served as controls. Our outcome measures encompassed the effect of insulin on pro-inflammatory mediators, the hepatic acute-phase-response, fat, and the IGF-I system. Results: Insulin administration decreased pro-inflammatory cytokines and proteins, while increasing constitutive-hepatic proteins (P < 0.05). Burned children receiving insulin required significantly less albumin substitution to maintain normal levels compared with control (P < 0.05). Insulin decreased free fatty acids and serum triglycerides when compared with controls (P < 0.05). Serum IGF-I and IGFBP-3 significantly increased with insulin administration (P < 0.05). Conclusion: Insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients. The systemic inflammatory and hepatic acute-phase-response contribute to hypermetabolism, multi-organ failure, and mortality. In the present study we show that insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.