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.
van der Poll
T
T
Center of Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center, University of Amsterdam, Netherlands.
van Deventer
S J
SJ
ten Cate
H
H
Levi
M
M
ten Cate
J W
JW
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009500:Neutralization Tests; D002679:Pan troglodytes; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D014115:Toxemia / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000276:immunology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli