Tumor necrosis factor and endotoxin induce similar metabolic responses in human beings.

HR Michie, DR Spriggs, KR Manogue, ML Sherman… - Surgery, 1988 - europepmc.org
HR Michie, DR Spriggs, KR Manogue, ML Sherman, A Revhaug, ST o'Dwyer, K Arthur…
Surgery, 1988europepmc.org
After injury, infection, or major operations a number of predictable metabolic responses
occur. It has been proposed that the cytokine tumor necrosis factor (TNF)/cachectin is a
primary mediator of these host responses. To test this hypothesis, we studied 16 tumor-
bearing humans with normal renal and hepatic function, who received 24-hour continuous
intravenous infusions of escalating doses of recombinant TNF (4 to 636/micrograms/m2/24
h). Serial measurements were made of vital signs and plasma concentrations of TNF …
After injury, infection, or major operations a number of predictable metabolic responses occur. It has been proposed that the cytokine tumor necrosis factor (TNF)/cachectin is a primary mediator of these host responses. To test this hypothesis, we studied 16 tumor-bearing humans with normal renal and hepatic function, who received 24-hour continuous intravenous infusions of escalating doses of recombinant TNF (4 to 636/micrograms/m2/24 h). Serial measurements were made of vital signs and plasma concentrations of TNF, interleukin-1, adrenocorticotropic hormone, cortisol, iron, glucose, and C-reactive protein. Low doses of TNF had minimal metabolic effects, but infusions of greater than or equal to 545 micrograms/m2/24 hr (n= 8) resulted in fever, pituitary, and stress hormone release and acute phase changes. These alterations were compared with the changes that occurred in healthy humans (n= 13) receiving intravenous bolus injections of Escherichia coli endotoxin (4 ng/kg). TNF infusion in doses greater than or equal to 545 micrograms/m2/24 hr produced peak plasma TNF concentrations and metabolic responses that were similar to those after endotoxin injection. Interleukin-1 concentrations remained basal after TNF or endotoxin administration. TNF may represent the primary afferent signal that initiates many of the metabolic responses associated with sepsis and endotoxemia.
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