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Experimental human endotoxemia as a model of systemic inflammation
Biochimie ( IF 3.3 ) Pub Date : 2018-06-22 , DOI: 10.1016/j.biochi.2018.06.014
Dirk van Lier , Christopher Geven , Guus P. Leijte , Peter Pickkers

Systemic inflammation plays a pivotal role in a multitude of conditions, including sepsis, trauma, major surgery and burns. However, comprehensive analysis of the pathophysiology underlying this systemic inflammatory response is greatly complicated by variations in the immune response observed in critically ill patients, which is a result of inter-individual differences in comorbidity, comedication, source of infection, causative pathogen, and onset of the inflammatory response. During experimental human endotoxemia, human subjects are challenged with purified endotoxin (lipopolysaccharide) intravenously which induces a short-lived, well-tolerated and controlled systemic inflammatory response, similar to that observed during sepsis. The human endotoxemia model can be conducted in a highly standardized and reproducible manner, using a carefully selected homogenous study population. As such, the experimental human endotoxemia model does not share the aforementioned clinical limitations and enables us to investigate both the mechanisms of systemic inflammation, as well as to evaluate novel (pharmacological) interventions in humans in vivo. The present review provides a detailed overview of the various designs, organ-specific changes, and strengths and limitations of the experimental human endotoxemia model, with the main focus on its use as a translational model for sepsis research.



中文翻译:

实验性人类内毒素血症作为全身性炎症的模型

全身性炎症在包括脓毒症,创伤,大手术和烧伤在内的多种疾病中起着关键作用。然而,由于在重症患者中观察到的免疫反应差异很大,对这种全身性炎症反应基础的病理生理学的综合分析非常复杂,这是由于合并症,喜剧,感染源,病原体和发病之间存在个体差异的结果炎症反应。在实验性人类内毒素血症期间,人类受试者会接受静脉内纯化的内毒素(脂多糖)攻击,从而诱发短暂的,良好耐受的和受控的全身性炎症反应,类似于脓毒症期间观察到的情况。人类内毒素血症模型可以高度标准化和可重复的方式进行,使用精心挑选的同质研究人群。因此,实验性人类内毒素血症模型没有上述临床局限性,使我们能够研究全身性炎症的机制,并评估对人类的新型(药理)干预措施体内。本综述提供了实验性人类内毒素血症模型的各种设计,器官特异性变化以及强度和局限性的详细概述,主要侧重于将其用作脓毒症研究的转化模型。

更新日期:2018-06-22
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