TNF-alpha has no direct in vivo metabolic effect on human muscle.
Tumor necrosis factor alpha (TNF-alpha) is thought to have a key role in metabolic changes of muscle tissue during inflammatory diseases. It is unknown whether TNF-alpha affects muscle metabolism directly or whether these changes are mediated by secondary mediators. We studied 6 patients undergoing isolated limb perfusion with TNF-alpha for irresectable soft-tissue sarcoma or in-transit melanomas. Glucose, lactate, ammonia and amino-acid consumption or production were measured in the perfusate during 3 perfusion periods: before, after TNF-alpha and after the combined administration of TNF alpha and melphalan. Arterial glucose, lactate, ammonia and amino-acid concentrations were monitored to detect metabolic effects of TNF-alpha after it entered the systemic circulation. Glucose uptake and lactate release by the limb remained unchanged after the injection of TNF-alpha alone, as well as after the combination of TNF-alpha and melphalan. Furthermore, glutamine, alanine, phenylalanine, tyrosine and total amino-acid release into the perfusate did not increase during TNF-alpha and melphalan treatment, indicating that muscle metabolism was not changed. After the isolated limb perfusion, TNF-alpha entered the systemic circulation and induced metabolic changes resulting in a doubling of arterial lactate concentrations, decreased arterial glucose concentrations and decreased arterial amino-acid concentrations. Our study shows that regional administration of TNF-alpha alone or in combination with melphalan does not directly affect muscle glucose and protein metabolism. The data suggest that systemic metabolic changes induced by TNF-alpha are mediated through secondary, centrally produced, factors.
De Blaauw
I
I
Department of Surgery, Maastricht University, The Netherlands.
Eggermont
A M
AM
Deutz
N E
NE
de Vries
M
M
Buurman
W A
WA
Von Meyenfeldt
M F
MF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000596:Amino Acids / Q000097:blood / Q000378:metabolism; D000641:Ammonia / Q000097:blood / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012509:Sarcoma / Q000188:drug therapy / Q000378:metabolism; D012983:Soft Tissue Neoplasms / Q000188:drug therapy / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D000596:Amino Acids; D018906:Antineoplastic Agents, Alkylating; D001786:Blood Glucose; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D000641:Ammonia; D005947:Glucose; D008558:Melphalan