In VivoEndotoxin Tolerance: Impaired LPS-Stimulated TNF Release of Monocytes from Patients with Sepsis, but Not SIRS

Abstract

In vitropretreatment of human monocytes (MO) with low-dose lipopolysaccharide (LPSp) inhibits TNF release in response to subsequent LPSaactivation. Septic patients are often indistinguishable from patients with systemic inflammatory response syndrome (SIRS). We hypothesized thatin vivoexposure to “septic” stimuli impairs subsequent LPSa-stimulated MO TNF productionin vitro.Human peripheral MO were obtained after informed consent from controls or patients with sepsis, SIRS, or posttrauma [ACCP/SCCM definitions]. Cells were platedin vitro,incubated 24 hr, and then stimulated with 0–1000 ng/ml LPSafor 4 hr. Parallel control MO were incubatedin vitrowith 100 ng/ml LPSpfor 24 hr and then stimulated with 1000 ng/ml LPSafor 4 hr. Supernatant TNF (mean U/ml ± SEM) was measured by bioassay. ANOVA was used to determine statistical significance.In vitroLPSppretreatment markedly inhibited subsequent LPSa-stimulated TNF release.In vitroLPSa-stimulated TNF release was likewise significantly inhibited with MO from septic patients compared to controls. Inhibition was more profound in septic patients with shock (not shown). No impaired TNF release was seen with MO from SIRS or trauma patients. In conclusion,in vivopreexposure to inflammatory stimuli in septic patients alters monocyte regulation in a manner similar toin vitroendotoxin tolerance. Provocativein vitromonocyte LPS stimulation may distinguish patients with sepsis and SIRS.