LPS-TOLERANCE IMPROVES SURVIVAL AND BACTERIAL CLEARANCE IN MICE WITH BURN WOUND INFECTIONS.

Objective: To determine if priming of mice with endotoxin following large surface area flame burns will improve resistance to wound infection. Methods: C57BL6 wild-type mice (6-8 wks old; female) received ?40% surface area burn under anesthesia. On days 02 & 04 post-burn, mice received an injection of LPS (1 μg/0.2 cc; I.P.) or saline. On day 05, all mice were challenged with lethal inocula of Pseudomonas aeruginosa. Skin biopsies were obtained at 48 hrs post-infection to determine the bacterial load in vivo. Additional mice were observed for mortality during the next 10 days. Results: Five days post-burn, LPS-tolerant mice had significantly fewer bacteria in burn wounds and significantly less mortality than control mice. Conclusions: Endotoxin tolerance induced after initial large burn insult significantly improved clearance of P. aeruginosa and reduced mortality compared to saline-treated mice. Supported by NIH-NIGMS and Shriners of North America