Tumor necrosis factor and the acute metabolic response to tissue injury in man.
Tumor necrosis factor and the acute metabolic response to tissue injury in man.
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DOI：
10.1172/jci113733
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发表时间：
1988-10
期刊：
影响因子：
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通讯作者：
H. F. Stames;R. S. Warren;M. Jeevanandam;J. Gabrilove;W. Larchian;H. Oettgen;Murray F. Brennan
中科院分区：
文献类型：
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作者：
H. F. Stames;R. S. Warren;M. Jeevanandam;J. Gabrilove;W. Larchian;H. Oettgen;Murray F. Brennan
肿瘤坏死因子（恶病素）是一种由单核细胞和巨噬细胞产生的蛋白质，被认为是内毒素休克和慢性感染恶病质致命效应的重要介质。作为抗肿瘤试验的一部分，重组人肿瘤坏死因子 α (rTNF) 被静脉注射给患者。单次注射 rTNF 后会出现发烧、心动过速以及较高剂量的低血压。 rTNF 给药后的代谢效应与剂量相关，包括随着二氧化碳产生增加而增加能量消耗，增加全身蛋白质代谢和前臂外周氨基酸流出，以及与血浆皮质醇显着增加相关的总动脉氨基酸水平降低。血清甘油三酯升高，甘油和游离脂肪酸周转增加，表明 rTNF 后全身脂肪分解和脂肪利用率增加。这些发现表明，给予人体 TNF 会重现许多对组织损伤的急性生理和代谢反应，包括能量底物动员。
Tumor necrosis factor (cachectin), a protein produced by monocytes and macrophages, has been implicated as an important mediator of the lethal effects of endotoxic shock and the cachexia of chronic infection. Recombinant human tumor necrosis factor alpha (rTNF) was given intravenously to patients as part of an antineoplastic trial. Fever, tachycardia, and at higher doses, hypotension occurred after a single injection of rTNF. Metabolic effects after rTNF administration were dose related and included enhanced energy expenditure with elevated CO2 production, increased whole body protein metabolism and peripheral amino acid efflux from the forearm, and decreased total arterial amino acid levels associated with a significant increase in plasma cortisol. Elevated serum triglycerides, as well as increased glycerol and free fatty acid turnover were seen, suggesting increased whole body lipolysis and fat utilization after rTNF. These findings indicate that administration of TNF in man reproduces many of the acute physiologic and metabolic responses to tissue injury, including energy substrate mobilization.