Diminished interferon-gamma production and responsiveness after endotoxin administration to healthy humans.
To obtain insight in the capacity of the lipopolysaccharide (LPS)-tolerant host to produce interferon (IFN)-gamma and to respond to this cytokine, whole blood was obtained from healthy humans before and 4 h after intravenous injection of LPS (4 ng/kg) and stimulated ex vivo. LPS exposure in vivo resulted in a diminished capacity to produce IFN-gamma after restimulation with LPS, together with a reduced ability to release the IFN-gamma-inducing cytokines interleukin (IL)-12 and IL-18 and with reduced responsiveness toward these cytokines. In addition, IFN-gamma responsiveness was strongly diminished after in vivo LPS exposure, as shown by the fact that blood obtained after LPS injection could not be primed by IFN-gamma for LPS-induced tumor necrosis factor-alpha release and that peripheral blood monocytes could not be stimulated by IFN-gamma to up-regulate major histocompatibility complex type II expression. Experimentally induced immunoparalysis is associated with strongly reduced IFN-gamma production and responsiveness.
Weijer
Sebastiaan
S
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. s.weijer@amc.uva.nl
Lauw
Fanny N
FN
Branger
Judith
J
van den Blink
Bernt
B
van der Poll
Tom
T
D000328:Adult; D015536:Down-Regulation; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007108:Immune Tolerance; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D018664:Interleukin-12 / Q000096:biosynthesis; D020382:Interleukin-18 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D009000:Monocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000949:Histocompatibility Antigens Class II; D020382:Interleukin-18; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma