Application of the model
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 are a result of inter-individual differences in comorbidity, comedication, source of infection, causative pathogen, and onset of the inflammatory response. This heterogeneity between patients impedes evaluation of pathophysiological mechanisms and hampers accurate comparison of (pharmacological) interventions. As a consequence, large numbers of patients need to be included in clinical trials to demonstrate intervention efficacy. Strikingly, even when these numbers were met, many of the positive results found in preclinical (animal) studies of systemic inflammation could not be reproduced in expensive (phase III) clinical trials. Therefore, an intermediate step is highly warranted to improve translation of preclinical animal data to sepsis patients.
The experimental human endotoxemia model can be used to overcome the aforementioned constraints of translating preclinical results into clinical practice.
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. 
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