Induction of IRAK-M Is Associated with Lipopolysaccharide Tolerance in a Human Endotoxemia Model

摘要: Recent in vitro and murine vivo studies have identified several potential LPS tolerance factors. In this study, we describe the expression kinetics of these factors standardized human endotoxemia models using i.v. bolus administration. Responsiveness to as well regulators signaling were determined peripheral whole blood. Intravenous administration (4 ng/kg) resulted peak plasma levels TNF-alpha at 1.5 h followed by subsequent peaks classic negative feedback inhibitors A20 IL-10 2 3 h, respectively. Circulating blood monocyte counts decimated during initial inflammatory response, but normalized period between 4 8 post-LPS. The response ex TNF release per was profoundly decreased 6-8 post-LPS injection despite cessation after h. Analysis MyD88short, IL-1R-associated kinase (IRAK)-1, IRAK-M, ST2, suppressor cytokine signaling-1 -3, SHIP-1, MAP phosphatase-1 indicated that observed associated with IRAK-1 elevated IRAK-M model. Interestingly, a lower dose (1 induced accompanied up-regulation without depletion IRAK-1. showed is largely dependent on TNF-alpha. rise transcription model appeared much greater compared vitro-stimulated conclusion, up-regulation.