Warren R S, Starnes H F, Gabrilove J L, Oettgen H F, Brennan M F
Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Arch Surg. 1987 Dec;122(12):1396-400. doi: 10.1001/archsurg.1987.01400240042007.
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.
有人提出，单核因子肿瘤坏死因子（TNF）（恶病质素）是恶性肿瘤常见的代谢异常的原因。研究了TNF对癌症患者的急性代谢影响。皮下注射重组人TNF导致C反应蛋白水平升高（4.4±1.2mg/dL对11.6±1.8mg/dL）和血清锌水平降低（12.9±0.8μmol/L对7.3±0.8μmol/L[79±5mg/dL对48±5mg/dL]）（数值为平均值±标准误）。静脉注射TNF后，前臂总氨基酸流出量增加了一倍多，主要是因为糖异生氨基酸丙氨酸和谷氨酰胺的释放增加。同时，丙氨酸、谷氨酰胺和总氨基酸的动脉水平下降，表明TNF也刺激了其他组织对氨基酸的摄取。观察到的氨基酸模式不能仅根据皮质醇、胰高血糖素或胰岛素水平的测量变化来解释。结合癌症相关恶病质中已知的氨基酸代谢改变对这些发现进行了讨论。
