IN-VIVO ENDOTOXIN TOLERANCE - IMPAIRED LPS-STIMULATED TNF RELEASE OF MONOCYTES FROM PATIENTS WITH SEPSIS, BUT NOT SIRS

In vitro pretreatment of human monocytes (MO) with low-dose lipopolysa ccharide (LPSp) inhibits TNF release in response to subsequent LPSa ac tivation. Septic patients are often indistinguishable from patients wi th systemic inflammatory response syndrome (SIPS). We hypothesized tha t in vivo exposure to ''septic'' stimuli impairs subsequent LPSa-stimu lated MO TNF production in vitro. Human peripheral MO were obtained af ter informed consent from controls or patients with sepsis, SIPS, or p osttrauma [ACCP/SCCM definitions]. Cells were plated in vitro, incubat ed 24 hr, and then stimulated with 0-1000 ng/ml LPSa for 4 hr. Paralle l control MO were incubated in vitro with 100 ng/ml LPSp for 24 hr and then stimulated with 1000 ng/ml LPSa for 4 hr. Supernatant TNF (mean U/ml +/- SEM) was measured by bioassay. ANOVA was used to determine st atistical significance. In vitro LPSp pretreatment markedly inhibited subsequent LPSa-stimulated TNF release. In vitro LPSa-stimulated TNF r elease was likewise significantly inhibited with MO from septic patien ts compared to controls. Inhibition was more profound in septic patien ts with shock (not shown). No impaired TNF release was seen with MO fr om SIPS or trauma patients. In conclusion, in vivo preexposure to infl ammatory stimuli in septic patients alters monocyte regulation in a ma nner similar to in vitro endotoxin tolerance. Provocative in vitro mon ocyte LPS stimulation may distinguish patients with sepsis and SIPS. ( C) 1997 Academic Press.