The acute metabolic effects of tumor necrosis factor administration in humans.
It has been suggested that the monokine tumor necrosis factor (TNF) (cachectin) is responsible for metabolic abnormalities frequently accompanying malignant neoplasms. The acute metabolic effects of TNF in patients with cancer were studied. Subcutaneous administration of recombinant human TNF led to a rise in the C-reactive protein level (4.4 +/- 1.2 mg/dL vs 11.6 +/- 1.8 mg/dL) and a reduction in the serum zinc level (12.9 +/- 0.8 mumol/L vs 7.3 +/- 0.8 mumol/L [79 +/- 5 mg/dL vs 48 +/- 5 mg/dL]) (values are the mean +/- SEM). Forearm efflux of total amino acids more than doubled after intravenous TNF injection, principally because of increases in release of the gluconeogenic amino acids alanine and glutamine. Concomitantly, the arterial levels of alanine, glutamine, and total amino acids fell, indicating that TNF also stimulated the uptake of amino acids by other tissues. The observed amino acid pattern cannot be explained solely on the basis of measured changes in cortisol, glucagon, or insulin levels. These findings are discussed in relation to known alterations of amino acid metabolism in cancer-associated cachexia.
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
R S
RS
Warren
H F
HF
Starnes
J L
JL
Gabrilove
H F
HF
Oettgen
M F
MF
Brennan
D000328:Adult; D000596:Amino Acids / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002100:Cachexia / Q000097:blood / Q000139:chemically induced; D004341:Drug Evaluation; D005260:Female; D005938:Glucocorticoids / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012107:Research Design; D012709:Serum Albumin / Q000032:analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D015032:Zinc / Q000097:blood
D000596:Amino Acids; D005938:Glucocorticoids; D011994:Recombinant Proteins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D015032:Zinc