Influence of endotoxin-induced acute lung injury on pulmonary innate and adaptive immunity

The aim of our study was to analyze pulmonary innate and adaptive immune responses during endotoxemia-induced acute lung injury (ALI).

Female BALB/c mice were challenged by endotoxin given intraperitoneally and followed for 24 h by unrestrained plethysmographic analysis. After this period, the mice were sacrificed by CO2 anesthesia and lung histopathology, pulmonary and serum levels of pro-inflammatory cytokines, numbers of lymphocyte subsets in blood and lung, and lung-derived macrophages (Mphi) were analyzed.

Animals with endotoxemia demonstrated significant depression of tidal volumes indicating respiratory failure compared to control mice. Lung histopathology of endotoxin-exposed animals revealed alveolar leakage characterizing ALI. Pulmonary levels of interleukin (IL)-1beta, IL-6 and interferon (IFN)-gamma in animals with endotoxemia were significantly elevated, whereas serum levels of IL-6 only were increased. IFN-gamma was strongly expressed by lung-derived Mphi with high CD11b expression, and this subset significantly increased in the lungs after endotoxin challenge. Additionally, the numbers of lung-resident CD4+ and total T-lymphocytes were significantly reduced after challenge.

These data suggest that endotoxemia-induced ALI is associated with exaggerated and sustained pulmonary innate immune responses partly mediated by activated Mphi, whereas adaptive immunity in the lungs is compromised.