title: TNF-alpha has no direct in vivo metabolic effect on human muscle.
abstract: 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.
authors.affiliation: Department of Surgery, Maastricht University, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: De Blaauw
authors.forename: A M
authors.initials: AM
authors.lastname: Eggermont
authors.forename: N E
authors.initials: NE
authors.lastname: Deutz
authors.forename: M
authors.initials: M
authors.lastname: de Vries
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.forename: M F
authors.initials: MF
authors.lastname: Von Meyenfeldt
mesh_terms: 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*
chemical_list: D000596:Amino Acids; D018906:Antineoplastic Agents, Alkylating; D001786:Blood Glucose; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; D000641:Ammonia; D005947:Glucose; D008558:Melphalan