Diminished Interferon-γ 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)–γ 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-γ after restimulation with LPS, together with a reduced ability to release the IFN-γ–inducing cytokines interleukin (IL)–12 and IL-18 and with reduced responsiveness toward these cytokines. In addition, IFN-γ 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-γ for LPS-induced tumor necrosis factor–α release and that peripheral blood monocytes could not be stimulated by IFN-γ to up-regulate major histocompatibility complex type II expression. Experimentally induced immunoparalysis is associated with strongly reduced IFN-γ production and responsiveness