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

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-alpha (TNF), interleukin (IL)-1beta, 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-1beta, 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.