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TNF‐α has no direct in vivo metabolic effect on human muscle
Author(s) -
De Blaauw Ivo,
Eggermont Alexander M.M.,
Deutz Nicolaas E.P.,
De Vries Marc,
Buurman Wim A.,
Von Meyenfeldt Maarten F.
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970410)71:2<148::aid-ijc4>3.0.co;2-0
Subject(s) - melphalan , medicine , endocrinology , tumor necrosis factor alpha , glutamine , metabolism , perfusion , carbohydrate metabolism , skeletal muscle , in vivo , glucose uptake , biology , chemistry , amino acid , biochemistry , chemotherapy , insulin , microbiology and biotechnology
Tumor necrosis factor alpha (TNF‐α) is thought to have a key role in metabolic changes of muscle tissue during inflammatory diseases. It is unknown whether TNF‐α affects muscle metabolism directly or whether these changes are mediated by secondary mediators. We studied 6 patients undergoing isolated limb perfusion with TNF‐α 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‐α and after the combined administration of TNFα and melphalan. Arterial glucose, lactate, ammonia and aminoacid concentrations were monitored to detect metabolic effects of TNF‐α after it entered the systemic circulation. Glucose uptake and lactate release by the limb remained unchanged after the injection of TNF‐α alone, as well as after the combination of TNF‐α and melphalan. Furthermore, glutamine, alanine, phenylalanine, tyrosine and total amino‐acid release into the perfusate did not increase during TNF‐α and melphalan treatment, indicating that muscle metabolism was not changed. After the isolated limb perfusion, TNF‐α 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‐α 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‐α are mediated through secondary, centrally produced, factors. Int. J. Cancer 71:148–154, 1997. © 1997 Wiley‐Liss, Inc.