Changes in endotoxin-induced cytokine production by whole blood after in vivo exposure of normal humans to endotoxin.
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.
van der Poll
T
T
Cornell University Medical College, Department of Surgery, New York, New York 10021, USA.
Coyle
S M
SM
Moldawer
L L
LL
Lowry
S F
SF
D000328:Adult; D001769:Blood / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007108:Immune Tolerance; D007375:Interleukin-1 / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014611:Vaccination / Q000379:methods*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10