Mahony S M, Beck S A, Tisdale M J
CRC Experimental Chemotherapy Group, Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.
Br J Cancer. 1988 Apr;57(4):385-9. doi: 10.1038/bjc.1988.87.
A comparison has been made of the cachectic effects produced by the transplantable murine adenocarcinoma of the mouse colon (MAC16) with tumour necrosis factor-alpha (cachectin). Tumour necrosis factor-alpha (TNF-alpha) produced a dose-related weight reduction that was accompanied by a decrease in both food and water intake. The degree of weight loss was directly proportional to the decreased food and water intake. In contrast weight loss produced by the MAC16 tumour occurred without a reduction in fluid or nutrient intake. Both the MAC16 tumour and TNF-alpha produced hypoglycaemia and a reduction in the circulatory level of free fatty acids (FFA), but had opposite effects on the level of plasma triglycerides with the MAC16 tumour-induced cachexia causing a decrease and TNF-alpha producing an increase. The MAC16 tumour elaborated a lipolytic factor which caused an immediate release of FFA from adipose tissue. In contrast TNF-alpha had no effect on mobilization of adipose triglycerides over a short time period. Both TNF-alpha and extracts from the MAC16 tumour caused an enhanced release of amino acids from mouse diaphragm, which was suppressible with indomethacin and heat labile. No TNF was detected in the MAC16 tumour or in the serum of tumour-bearing animals. Both tumour and non-tumour-bearing animals responded with a similar elevation of their serum TNF levels 90 min after a single injection of endotoxin. It is concluded that weight loss produced by TNF-alpha arises from an anorexic effect and that this differs from the complex metabolic changes associated with cancer cachexia.
已对小鼠结肠可移植性鼠腺癌（MAC16）与肿瘤坏死因子-α（恶病质素）产生的恶病质效应进行了比较。肿瘤坏死因子-α（TNF-α）产生了与剂量相关的体重减轻，同时伴有食物和水摄入量的减少。体重减轻的程度与食物和水摄入量的减少直接成正比。相比之下，MAC16肿瘤导致的体重减轻并未伴随着液体或营养物质摄入量的减少。MAC16肿瘤和TNF-α均导致低血糖和循环中游离脂肪酸（FFA）水平降低，但对血浆甘油三酯水平的影响相反，MAC16肿瘤诱导的恶病质导致甘油三酯水平降低，而TNF-α则使其升高。MAC16肿瘤产生一种脂解因子，可导致脂肪组织立即释放FFA。相比之下，TNF-α在短时间内对脂肪甘油三酯的动员没有影响。TNF-α和MAC16肿瘤提取物均导致小鼠膈肌氨基酸释放增加，吲哚美辛可抑制这种增加，且该作用对热不稳定。在MAC16肿瘤或荷瘤动物血清中未检测到TNF。单次注射内毒素90分钟后，肿瘤动物和非肿瘤动物血清TNF水平均有类似升高。结论是，TNF-α导致的体重减轻源于厌食效应，这与癌症恶病质相关的复杂代谢变化不同。
