Increased release of soluble tumor necrosis factor receptors into blood during clinical sepsis
W. Ertel, F. A. Scholl, H. Gallati, M. Bonaccio, F. W. Schildberg and O. Trentz
Department of Surgery, University of Zurich, Switzerland.
OBJECTIVES: To examine the kinetics of altered soluble tumor necrosis
factor receptors (sTNFRs) released in patients with severe sepsis, their
correlation with the morbidity and mortality of these patients, and the
role of endotoxin to induce cleavage of sTNFRs. DESIGN: Soluble TNFR levels
in plasma obtained from 40 patients with severe sepsis (mean [+/- SD] Acute
Physiology and Chronic Health Evaluation [APACHE] II score, 27.9 +/- 7.0
points) on days 0, 1, 3, 5, and 10 after sepsis diagnosis were measured
using specific enzyme-linked immunological binding assays and compared with
levels in 75 control patients without infection. In addition, an ex vivo
model consisting of lipopolysaccharide stimulation of human whole blood as
a relevant physiological milieu was used. Blood from patients with sepsis
and control patients was incubated 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 determined 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 those of control patients, and correlated
(P < .001) with the simultaneously obtained APACHE II and multiple organ
failure scores, as well as with mortality. Although incubation of whole
blood with lipopolysaccharide increased the release of sTNFR p55 and p75 in
both groups, sTNFR concentrations in blood from control patients remained
low compared with those of patients with severe sepsis, despite stimulation
of whole blood with a maximum lipopolysaccharide concentration.
CONCLUSIONS: These data indicate that an enhanced release of sTNFRs during
severe sepsis is not solely induced by endotoxin. Since the degree of
increased sTNFR levels portended poorly for patient survival, elevated
sTNFR levels may represent a good marker for severity of sepsis, thus
predicting outcome.
