Experimental human endotoxemia: a model of the systemic inflammatory response syndrome?
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.
Department of Surgery, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. calvanst@umdnj.edu
Steve E
SE
Calvano
Susette M
SM
Coyle
D000293:Adolescent; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D039481:CD11b Antigen / Q000097:blood; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004731:Endotoxins; D004837:Epinephrine / Q000097:blood; D004926:Escherichia coli; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D008954:Models, Biological; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D056152:Respiratory Rate / Q000187:drug effects; D018746:Systemic Inflammatory Response Syndrome / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000819:agonists
D039481:CD11b Antigen; D016207:Cytokines; D004731:Endotoxins; C509295:ITGAM protein, human; D008070:Lipopolysaccharides; D047889:Receptors, Tumor Necrosis Factor, Type II; D051197:Toll-Like Receptor 4; C044101:endotoxin, Escherichia coli; D006854:Hydrocortisone; D004837:Epinephrine