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Updated: May 17, 2026
Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Experimental human endotoxemia: a model of the systemic inflammatory response syndrome?
Steve E Calvano1, Susette M Coyle
1Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. calvanst@umdnj.edu
Background:
The normal human intravenous endotoxin model has been used for more than 50 years. It was once considered a possible model of sepsis, but, because no infection is present, it is better described as a model of systemic inflammation. We demonstrate herein that at least three of four systemic inflammatory response syndrome (SIRS) criteria are achieved with the model.
Methods:
Otherwise healthy human volunteers were given Escherichia coli endotoxin 2 ng/kg intravenously. Vital signs were monitored, and blood samples were collected over time for assessment of white blood cells (WBCs), cytokines, counter-regulatory hormones, and monocyte receptors.
Results:
The means of three variables (core temperature, heart rate, WBC) met the SIRS criteria. Compared with baseline, cytokines were elevated acutely, with tumor necrosis factor-alpha (TNFα) exhibiting temporal primacy over the other cytokines. Counter-regulatory hormones (cortisol, epinephrine) also were elevated acutely. Finally, the monocyte cell-surface receptors cluster of differentiation molecule (CD) 11b and TNF receptor-II were elevated and decreased, respectively.
Conclusions:
The experimental human endotoxin model satisfies SIRS criteria and probably is best described as a model of Toll-like receptor 4 agonist-induced systemic inflammation.
