Inhalation injury causes recruitment of IL-12lo neutrophils late after injury

Abstract

Abstract Inhalation injury causes increased morbidity and a 20% increase in mortality following burn injury. Although it is known that inhalation injury causes immune dysfunction among patients, few animal models of inhalation injury examine changes in the immune profile following inhalation injury. Our lab generated a clinically relevant murine model using female C57BL/6 mice (8–12 weeks, >18g) that were intubated and subjected to a woodsmoke inhalation injury. Additionally, a subset of mice were subjected to a combined injury consisting of inhalation and burn injury (20% total body surface area). Increased mortality was only observed following combined injury (50% mortality within 5 days of injury, p<0.05). Inhalation injury alone caused significant weight loss, peaking at 14 days post injury (p<0.05). Bronchioalveolar lavage (BAL) performed 16 days post injury demonstrated increased cell recruitment following inhalation injury (1.5 fold, p=0.15) and combined injury (2.4 fold, p<0.05) compared to sham controls. Cells recruited to the airway were identified as neutrophils and macrophages by flow cytometry. Intracellular staining demonstrated that neutrophils, but not macrophages, exhibited decreased expression of IL-10 and IL-12 following inhalation or combined injury. In our model, inhalation injury and combined injury cause cellular recruitment to the lungs and decreased production of cytokines known to be important for immune function. Thus we propose to use this model as a means to determine if changes to neutrophil activity contribute to increased susceptibility to bacterial infections and poor outcomes following inhalation or combined injury.