Dept. of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Dept. of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Biochimie. 2019 Apr;159:99-106. doi: 10.1016/j.biochi.2018.06.014. Epub 2018 Jun 22.
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.
全身性炎症在多种情况下发挥着关键作用，包括败血症、创伤、大手术和烧伤。然而，由于危重病患者的免疫反应存在个体差异，这种全身性炎症反应的病理生理学的全面分析变得非常复杂，这些差异是由合并症、合并用药、感染源、病原体和炎症反应的发生的个体差异引起的。在实验性人体内毒素血症中，通过静脉内给予纯化的内毒素（脂多糖）来挑战人体，从而诱导短暂、耐受良好且受控的全身性炎症反应，类似于败血症期间观察到的反应。人体内毒素血症模型可以采用精心选择的同质研究人群以高度标准化和可重复的方式进行。因此，实验性人体内毒素血症模型没有上述临床限制，并使我们能够在体内研究全身性炎症的机制，以及评估新型（药物）干预措施。本文综述详细概述了实验性人体内毒素血症模型的各种设计、器官特异性变化以及优缺点，主要侧重于将其作为败血症研究的转化模型的应用。
