Endogenous lipoproteins impact the response to endotoxin in humans

Critical Care Medicine
Hobart W HarrisStephen J Wigmore

Abstract

To determine whether endogenous lipoproteins can abrogate the host response to lipopolysaccharide (LPS) in vivo. Randomized, placebo-controlled study. Urban public hospital with academic affiliation. Eighteen healthy, normolipidemic, normal weight volunteers, 21-35 yrs of age. Fasting and postprandial (hypertriglyceridemic) subjects were injected with endotoxin (LPS, Lot EC-5, 4 ng/kg = 20 endotoxin units/kg) as either a bolus or following preincubation of the LPS with autologous whole blood vs. saline. In addition, LPS-induced cytokine production was determined ex vivo to examine the capacity of fasting vs. hypertriglyceridemic whole blood to attenuate the effect of large, potentially lethal concentrations of LPS in humans. Vital signs were recorded and serial blood samples analyzed for changes in white blood cell count, cytokine, and stress hormone levels over 24 hrs. The distribution of lipoproteins in fasting and postprandial blood after preincubation was determined using 125I-LPS. Endogenous lipoproteins abrogated the host response to LPS in vivo, but only after preincubation with the LPS. Peak oral temperature (p < .05) and white blood cell count (p < .05), and plasma tumor necrosis factor (TNF)-alpha (p < .01) and adreno...Continue Reading

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