Inflammatory Responses To Bronchial Endotoxin Instillati

给人内毒素允许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是重要的，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，将评估将内毒素直接注入肺亚段的效果。内毒素注入后2、6、24、48或72小时依次进行支气管肺泡灌洗。分析内容包括：支气管肺泡灌洗检测急性期细胞因子；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期细胞因子释放，骨髓细胞募集和急性期蛋白质释放的开始。肺泡血液界面的体外双层模型已被设计，以促进发现机制，招募炎症细胞到肺。这些观察结果将有助于确定细菌内毒素引起的急性肺部炎症的开始和解决的重要事件。

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.