RESPONSE OF MAN TO ENDOTOXIN
RESPONSE OF MAN TO ENDOTOXIN
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DOI：
10.1016/s0171-2985(11)80353-0
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发表时间：
1993-04-01
期刊：
影响因子：
2.8
通讯作者：
SUFFREDINI, AF
中科院分区：
文献类型：
--
作者：
MARTICH, GD;BOUJOUKOS, AJ;SUFFREDINI, AF
内毒素是革兰氏阴性菌的细胞壁成分，在感染性休克的发病机制中起核心作用。通过给人小剂量静脉注射内毒素，可诱导各种急性炎症反应，其性质与感染性休克早期发生的反应相似。志愿者静脉注射内毒素后数小时内，全身血流动力学、心室功能、肺气体交换和渗透性发生改变。与这些器官功能的变化相结合，多种炎症介质被释放，这些介质似乎有助于这些反应。这些包括促炎细胞因子的释放（如肿瘤坏死因子α、il -1 β、IL-6、IL-8）、纤溶系统的激活、钾化钾激肽的生成和磷脂酶A2的释放。吞噬白细胞在内毒素给药后会增强炎症反应。反调节反应是平行启动的，可能用于限制炎症介质的一些终末器官反应。这种人体模型提供了一个独特的机会来扩展以前的急性炎症概念，并评估暴露于重要细菌成分后激活的最早反应。确定急性人类内毒素血症期间启动的途径和反应可能有助于更好地理解宿主反应，这些反应对严重感染引起的器官功能障碍和休克的发展至关重要。
Endotoxin, a cell wall component of Gram-negative bacteria, plays a central role in the pathogenesis of septic shock. By administering small doses of intravenous endotoxin to humans, a variety of acute inflammatory responses are induced which are qualitatively similar to those that occur during the early stages of septic shock. Within hours of the administration of intravenous endotoxin to human volunteers, changes occur in systemic hemodynamics, ventricular function, pulmonary gas exchange and permeability. In conjunction with these changes in organ function, a wide variety of inflammatory mediators are released which appear to contribute to these responses. These include the release of proinflammatory cytokines (e.g. tumor necrosis factor-alpha, IL-1beta, IL-6, IL-8), activation of the fibrinolytic system, kallikrein-kinin generation and phospholipase A2 release. Phagocytic leukocytes are primed for enhanced inflammatory responses following endotoxin administration. Counter-regulatory responses are initiated in parallel and may serve to limit some of the end-organ responses by the inflammatory mediators. This human model provides a unique opportunity to extend previous concepts of acute inflammation and to evaluate the earliest responses activated after exposure to an important bacterial component. Defining the pathways and responses initiated during acute human endotoxemia may allow a better understanding of host responses that are critical to the development of organ dysfunction and shock due to severe infections.