Tumor necrosis factor is involved in the appearance of interleukin-1 receptor antagonist in endotoxemia.

To assess the role of tumor necrosis factor (TNF) in the appearance of interleukin-1 receptor antagonist (IL-1RA) in endotoxemia, 4 healthy humans were studied after a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). In addition, 8 healthy chimpanzees were investigated after a bolus intravenous injection of Escherichia coli endotoxin (4 ng/kg) with (n = 4) or without (n = 4) a simultaneous intravenous injection of a monoclonal anti-TNF antibody (15 mg/kg). TNF induced a pronounced rise in IL-1RA concentrations, becoming apparent after 1 h and peaking after 3 h (P < .05). The rise in IL-1RA after administration of endotoxin started 2 h later. Neutralization of the early endotoxin-induced TNF activity by anti-TNF caused a marked reduction in IL-1RA concentrations (P < .05). These results indicate that TNF is an intermediate factor in IL-1RA release in endotoxemia.