The influence of human endotoxemia on CD95-induced apoptosis

Background: The responses of monocyte and neutrophil tumor necrosis factor receptor type 1 (TNFR-1) and TNFR-2 during systemic inflammation have been described previously. Several other members of the TNFR superfamily also ap pear to have regulatory roles in immunocyte function, including apoptosis. However, the response of these other receptor members, such as CD95, to sys temic inflammation is unclear. Objectives: To compare the response of CD95 with that of TNFR during system ic inflammation and to assess the influence of the inflammatory milieu on C D95 function. Setting: Adult clinical research center of a university hospital. Subjects and Methods: Five healthy male subjects were administered intraven ous endotoxin (2 ng/kg), and systemic response was measured by cytokine ana lysis and receptor expression assays during a 48-hour period. CD95 function during systemic inflammation was assessed using a Jurkat cell bioassay for degree of apoptosis. Results: Monocyte and neutrophil CD95 expression exhibited changes parallel to that of TNFR following endotoxin injection. In contrast to soluble TNFR , which was transiently elevated during endotoxemia, soluble CD95 levels re mained unchanged from baseline. Jurkat cells incubated in normal and posten dotoxin serum samples equally exhibited less than 10% spontaneous apoptosis . No soluble CD95 ligand was detectable in experimental human endotoxemia. Conclusions: Cell-associated CD95 exhibited changes parallel to its recepto r family member TNFR following endotoxin administration. Soluble CD95 is pr esent in human serum samples, but the levels remained unchanged following e ndotoxin administration. No soluble CD95 ligand activity was detectable by enzyme-linked immunosorbent assay or by functional assay. The potential pro tective role of soluble CD95 in human serum samples against CD95 ligand-ind uced apoptosis remains to be defined.