Insulin increases resistance to burn wound infection-associated sepsis

OBJECTIVE: This study was designed to determine the ability of insulin to improve outcome following a Pseudomonas aeruginosa wound infection in a rodent model of severe burn injury. BACKGROUND: Severe burn injury predisposes patients to burn wound infections that can disseminate, lead to uncontrolled inflammation, and induce septic shock. Whereas insulin administration has been extensively discussed to improve morbidity and mortality in critically ill patients, the ability of insulin to improve outcomes of severely burned patients with infected burn wounds is not known. DESIGN: Sprague-Dawley rats. SETTING: University setting. INTERVENTION: Burn-injured Sprague Dawley rats were randomized into treatment groups that received either saline or insulin. Burn wounds were topically inoculated with a lethal dose of Pseudomonas aeruginosa 6 days after injury. MEASUREMENTS AND MAIN RESULTS: Survival, systemic dissemination of bacteria, systemic inflammation, and immune activation were examined. Insulin decreased the early inflammatory response to a severe burn injury. Treatment with low doses of insulin following burn injury improved the outcome of rats in response to a lethal burn wound infection. Specifically, survival was improved and systemic dissemination of bacteria from the wound was decreased. Systemic inflammation, indicated by serum interleukin-6 levels, was significantly decreased by insulin treatments after injury. Additionally, insulin treatments were associated with alterations in B and T lymphocyte responses to wound infection. CONCLUSIONS: Although the mechanisms by which insulin improves outcome following a lethal burn wound infection are not known, the data suggest that immunologic responses to infection may be altered by postburn insulin treatments.