Inflammatory Responses to Bronchial Endotoxin Instillation in Humans

给人类注射内毒素可以用一种独特的方法来评估感染期间发生的早期炎症反应。表征这些反应和控制它们的机制很重要，因为这些炎症反应有助于感染性休克和器官衰竭的发展。根据92-CC-0141方案，将评估内毒素直接注入肺亚节段的效果。在内毒素滴注后2、6、24、48或72小时进行连续的支气管肺泡灌洗。分析将包括以下内容：急性时相细胞因子的支气管肺泡灌洗；中性粒细胞和淋巴细胞亚群的流式细胞术；全身和炎症效应，包括急性时相细胞因子释放、骨髓细胞募集和急性时相蛋白释放的启动。肺泡血液界面的体外双层模型已被设计用于促进发现将炎性细胞招募到肺内的机制。这些观察将有助于确定细菌内毒素引起的急性肺部炎症的启动和消退的重要事件。

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.