Experimental human endotoxemia as a model of systemic inflammation

• Published in: Biochimie Vol. 159; pp. 99 - 106
• Main Authors: van Lier, Dirk, Geven, Christopher, Leijte, Guus P., Pickkers, Peter
• Format: Journal Article
• Language: English
• Published: France Elsevier B.V 01.04.2019
• Subjects: Endotoxemia - chemically induced; Endotoxemia - metabolism; Endotoxemia - pathology; Experimental human endotoxemia; Humans; Innate immunity; Lipopolysaccharide; Lipopolysaccharides - chemistry; Lipopolysaccharides - toxicity; Models, Biological; Nontherapeutic Human Experimentation; Sepsis; Systemic inflammatory response; Translational research; Lipopolysaccharide; Systemic inflammatory response; Sepsis; Innate immunity; Translational research; Experimental human endotoxemia
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2018.06.014

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. •Experimental human endotoxemia induces a systemic innate immune response (74).•Highly standardized: facilitates between-subject and intervention-based comparisons (85).•Inflammation-induced organ dysfunction largely comparable to sepsis (70).•In vivo model, bridging the gap between preclinical studies and clinical research (83).