title: Hormonal and metabolic response to recombinant human tumor necrosis factor in rat: in vitro and in vivo.
abstract: Tumor necrosis factor (TNF; cachectin) has been implicated as a mediator of the toxic manifestations of overwhelming bacterial infection as well as the chronic catabolic state of cancer cachexia. We have examined the acute metabolic and hormonal response after administration of recombinant human TNF in the rat. TNF given by intraperitoneal injection produced dose- and time-related increases in hepatic amino acid uptake, decreases in serum trace metal concentrations, and a pattern of endocrine hormone alterations characteristic of the acute phase response to tissue injury. In vitro zinc transport studies by rat hepatocytes cultured in the presence of TNF alone, or in combination with recombinant human interleukin 1, another mediator of the acute phase response, demonstrated that neither monokine was capable of directly stimulating zinc transport into cells. These findings suggest that TNF may function as an endogenous mediator of the early metabolic response to sepsis and that the trace metal changes induced by TNF in vivo may occur through a secondary mechanism.
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005934:Glucagon / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015032:Zinc / Q000097:blood
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D007375:Interleukin-1; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D005934:Glucagon; D015032:Zinc