Serum levels of the apoptosis-associated molecules, tumor necrosis factor-alpha/tumor necrosis factor type-I receptor and Fas/FasL, in sepsis.

Abstract

STUDY OBJECTIVE: s: Numerous reports suggest that apoptosis may play an important role in the sepsis syndrome. The objective of the present study was to examine the levels of molecules associated with apoptosis belonging to the tumor necrosis factor (TNF)-alpha/TNF type-I receptor (TNFRI) and Fas ligand (FasL)/Fas receptor (Fas) pathways in patients with sepsis. PATIENTS AND METHODS: Twenty-two patients with sepsis (14 patients with severe sepsis and 8 patients with sepsis), and 6 healthy volunteers were evaluated. Sequential analysis of the serum levels of TNF-alpha, TNFRI, FasL, and Fas were performed in these patients using enzyme-linked immunosorbent assays. RESULTS: Detectable levels of TNF-alpha were found in only 8 of 14 patients with severe sepsis. Patients with severe sepsis and sepsis had similarly increased levels of FasL, compared with healthy individuals (p < 0.05). Higher levels of TNFRI and Fas were found in patients with severe sepsis than in patients with sepsis and healthy volunteers (p < 0.001 and p < 0.01, respectively). Fas levels were also higher in patients who died than in those who survived (p < 0.01). A direct relationship was found between serum levels of TNFRI and Fas, and multiorgan dysfunction (sequential organ failure assessment score) [p < 0.0001]. CONCLUSIONS: These results suggest that the TNF-alpha/TNFRI and FasL/Fas systems may be involved in the pathogenesis of sepsis. Serum levels of the death-receptors, TNFRI and Fas, could serve as potential markers of the severity of human sepsis.