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Changes in Endotoxin-Induced Cytokine Production by Whole Blood after in vivo Exposure of Normal Humans to Endotoxin

Tom van der Poll, Susette M. Coyle, Lyle L. Moldawer and Stephen F. Lowry
The Journal of Infectious Diseases
Vol. 174, No. 6 (Dec., 1996), pp. 1356-1360
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30129974
Page Count: 5
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Changes in Endotoxin-Induced Cytokine Production by Whole Blood after in vivo Exposure of Normal Humans to Endotoxin
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Abstract

Whole blood of 6 healthy subjects, who were intravenously injected with lipopolysaccharide (LPS, 2 ng/kg), was stimulated ex vivo with LPS (10 ng/mL). Three and 6 h after injection of LPS, whole blood produced less tumor necrosis factor-α (TNF), interleukin (IL)-1β, IL-6, and IL-10 (all P < .05). By contrast, the production of IL-1 receptor antagonist was enhanced after LPS injection (P < .05). Plasma obtained 2 h, but not 1 h, after in vivo administration of LPS showed a dose-dependent inhibition of TNF, IL-1β, and IL-6 production by LPS-stimulated whole blood from 6 other healthy donors not previously exposed to LPS, while the production of IL-10 and IL-1 receptor antagonist were not or were marginally influenced. LPS tolerance represents a purposeful adaptation of the host, rather than a generalized hyporesponsiveness, and is at least partly mediated by soluble factors produced within 2 h after previous exposure to LPS.

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