Impaired ex vivo lipopolysaccharide-stimulated whole blood tumor necrosis factor production may identify "septic" intensive care unit patients

Currently, there is no reliable diagnostic test: to identify septic intensi ve care unit (ICU) patients. We initiated studies to test the hypothesis th at in sepsis, the in vivo exposure to endotoxin is detectable by the ex viv o analysis of lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TN F) production. We obtained heparinized whole blood (WB) from 58 ICU patient s and 14 healthy controls. The samples were incubated +/-10 ng/mL of LPS at 37 degreesC for 3 h. Plasma TNF levels were measured using enzyme-linked i mmunoassay (mean +/- standard error of the mean). Clinical data, including ICU length of stay (LOS), ventilator days (VentD), WBC, and positive cultur es (Clt+), were obtained retrospectively. A wide range of LPS-stimulated WE TNF production (pg/mL) was observed in ICU patients (4481 +/- 469) and con trols (6706 +/- 715). Patients were stratified into quartiles (I-IV) on the basis of the distribution of plotted LPS-stimulated TNF values (pg/mL). Pa tients in quartile I (N = 14) had significantly lower TNF production (< 200 0 pg/mL, P < 0.05) and required increased VentD (16 vs. 10 days, P < 0.05) compared to quartiles Ii-IV (N = 44). Patients in quartile I also had a hig her incidence of infection (79 vs. 50%) and longer LOS (18 vs. 13 d) compar ed to quartiles Ii-IV. Impaired TNF release may be a manifestation of monoc yte endotoxin tolerance and may be useful to diagnose sepsis.