INCREASED RELEASE OF SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTORS INTO BLOOD DURING CLINICAL SEPSIS

Objectives: To examine the kinetics of altered soluble tumor necrosis factor receptors (sTNFRs) released in patients with severe sepsis, the ir correlation with the morbidity and mortality of these patients, and the role of endotoxin to induce cleavage of sTNFRs. Design: Soluble T NFR levels in plasma obtained from 40 patients with severe sepsis (mea n [+/-SD] Acute Physiology and Chronic Health Evaluation [APACHE] II s core, 27.9+/-7.0 points) on days 0, 1, 3, 5, and 10 after sepsis diagn osis were measured using specific enzyme-linked immunological binding assays and compared with levels in 75 control patients without infecti on. In addition, an ex vivo model consisting of lipopolysaccharide sti mulation of human whole blood as a relevant physiological milieu was u sed. Blood from patients with sepsis and control patients was incubate d in the presence or absence of lipopolysaccharide (1 mg/L) for 0, 1, 2, 4, 8, and 24 hours. Plasma levels of sTNFRs from both groups were d etermined using the enzyme-linked immunological binding assays.Results : In patients with sepsis, plasma levels of both sTNFRs were markedly (P<.01) increased during the whole observation period, compared with t hose of control patients, and correlated (P<.001) with the simultaneou sly obtained APACHE II and multiple organ failure scores, as well as w ith mortality. Although incubation of whole blood with lipopolysacchar ide increased the release of sTNFR p55 and p75 in both groups, sTNFR c oncentrations in blood from control patients remained low compared wit h those of patients with severe sepsis, despite stimulation of whole b lood with a maximum lipopolysaccharide concentration. Conclusions: The se data indicate that an enhanced release of sTNFRs during severe seps is is not solely induced by endotoxin. Since the degree of increased s TNFR levels portended poorly for patient survival, elevated sTNFR leve ls may represent a good marker for severity of sepsis, thus predicting outcome.