Is Circulating Tumor Necrosis Factor Bioactive?

To the Editor: Michie et al. (June 9 issue)¹ report the detection of circulating tumor necrosis factor after endotoxin administration and discuss its relation to clinical sequelae. However, some question remains about the identity of the molecule detected by their plasma assay and its pathophysiologic role, since they apparently did not perform assays of the subjects' plasma samples for tumor necrosis factor bioactivity. The discrepancy between the bioactivity of tumor necrosis factor and enzyme-linked immunosorbent assay (ELISA) reactivity is well established.² Both tumor necrosis factor and lymphotoxin have been shown to lose their biologic activity at a faster rate than.