Administration of endotoxin to humans allows a unique way to evaluate the early inflammatory reactions that occur during infection. Characterizing these responses and the mechanisms that control them is important because these inflammatory responses contribute to the development of septic shock and organ failure. In subjects enrolled in protocol 92-CC-0141, we will measure exhaled nitric oxide in endotoxin-challenged lung segments using balloon catheters at 2, 6, 24, or 48 hours after endotoxin instillation. Epithelial cell brushings will be performed to evaluate changes in the regulation of nitric oxide synthase activity during acute lung inflammation. In separate studies endobronchial biopsies will be performed after the instillation of endotoxin at 6 or 24 hours to provide tissue for in situ hybridization for early response gene activation.
