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-a (TNF), interleukin (lL)-lβ, IL-6, and IL-10 (all P < .05). By contrast, the production of IL-l 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 dosedependent 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-lO and IL-l 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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