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December 1998

The Influence of Human Endotoxemia on CD95-Induced Apoptosis

Author Affiliations

From the Department of Surgery, Division of Surgical Sciences, Robert Wood Johnson Medical School, New Brunswick, NJ (Drs Lin, Calvano, Randhawa, and Lowry, Ms Coyle, and Messrs Shahin and Kumar) and the Department of Surgery, New York University Medical Center, New York (Dr Katz).

Arch Surg. 1998;133(12):1322-1327. doi:10.1001/archsurg.133.12.1322

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 appear to have regulatory roles in immunocyte function, including apoptosis. However, the response of these other receptor members, such as CD95, to systemic inflammation is unclear.

Objectives  To compare the response of CD95 with that of TNFR during systemic inflammation and to assess the influence of the inflammatory milieu on CD95 function.

Setting  Adult clinical research center of a university hospital.

Subjects and Methods  Five healthy male subjects were administered intravenous endotoxin (2 ng/kg), and systemic response was measured by cytokine analysis 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 remained unchanged from baseline. Jurkat cells incubated in normal and postendotoxin 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 receptor family member TNFR following endotoxin administration. Soluble CD95 is present in human serum samples, but the levels remained unchanged following endotoxin administration. No soluble CD95 ligand activity was detectable by enzyme-linked immunosorbent assay or by functional assay. The potential protective role of soluble CD95 in human serum samples against CD95 ligand–induced apoptosis remains to be defined.