Burn Injury Induces Intestinal Inflammatory Response Mediated by Th17 in Burn-Primed Endotoxemic Mice

Abstract

Objective This study aimed to elucidate the mechanism underlying the susceptibility to infection-related acute lung injury by focusing on the role of gut mucosal T-helper (Th) 17 cells that preferentially produce IL-17 with probiotics in a burn-primed endotoxemic mice model. Methods Mice were subjected to a 15% total body surface area third-degree burn. Survival from lethal lipopolysaccharide (LPS) administration (3 mg/kg) on 11th day post-burn was assessed in mice fed by chow with or without 1.2% Lactobacillus powder after burn injury. Lamina propria mononuclear cells were enzymatically isolated from the ileum removed on 11th day post-burn and incubated along with 1 μg/mL LPS or 10 μg/mL anti-CD3 antibody for 24 hours; subsequently, the following 7 cytokines were analyzed in the supernatant: IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17. Results Lactobacillus treatment post-burn injury markedly improved survival after lethal endotoxemia in burn-primed mice (64.3% versus 21.4%, P = 0.03). The production of proinflammatory cytokines such as TNF-α, IL-6, and IL-17 by lamina propria mononuclear T-lymphocytes and macrophages including Th17 response was augmented by burn injury but decreased with Lactobacillus treatment after burn injury. Conclusions Th17- and Th17-mediated inflammatory responses in the gut mucosa may play a vital role, which could be attenuated by Lactobacillus treatment, in survival of lethal endotoxemia in burn-primed mice.