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. Under protocol 92-CC-0141, the effects of direct instillation of endotoxin into lung subsegments will be evaluated. Sequential bronchoalveolar lavage will be performed at 2, 6, 24, 48, or 72 hours after endotoxin instillation. Analyses will include the following: bronchoalveolar lavage for acute phase cytokines; flow cytometry of neutrophils and lymphocyte subpopulations; and systemic and inflammatory effects including acute phase cytokine release, recruitment of cells from the marrow and the initiation of acute phase protein release. An in vitro bilayer model of the alveolar blood interface has been designed to facilitate discovery of mechanisms that recruit inflammatory cells to the lung. These observations will be useful in defining important events in the initiation and resolution of acute lung inflammation to bacterial endotoxin.
| Hoen, Anne Gatewood; Margos, Gabriele; Bent, Stephen J et al. (2009) Phylogeography of Borrelia burgdorferi in the eastern United States reflects multiple independent Lyme disease emergence events. Proc Natl Acad Sci U S A 106:15013-8 |
| Luca, Rudolf; Lijnen, H Roger; Suffredini, Anthony F et al. (2002) Increased angiostatin levels in bronchoalveolar lavage fluids from ARDS patients and from human volunteers after lung instillation of endotoxin. Thromb Haemost 87:966-71 |
| O'Grady, N P; Preas, H L; Pugin, J et al. (2001) Local inflammatory responses following bronchial endotoxin instillation in humans. Am J Respir Crit Care Med 163:1591-8 |
