Rivadeneira D E, Naama H A, McCarter M D, Fujita J, Evoy D, Mackrell P, Daly J M
Department of Surgery, New York Presbyterian Hospital-Cornell Campus, NY, USA.
Nutr Cancer. 1999;35(2):202-6. doi: 10.1207/S15327914NC352_16.
Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating glucocorticoids and interleukin-6 (IL-6) have been observed in cancer patients with cachexia and are implicated as major mediators in this process. The purpose of this study was to investigate the role of circulating glucocorticoid levels as primary mediators in cancer-induced cachexia. We evaluated whether inhibition of glucocorticoids with the receptor antagonist RU-486 could abrogate the detrimental wasting of muscle and adipose tissues seen in a well-characterized murine tumor-induced cachexia model. Mice (12/group) were randomized to control, tumor-bearing, control + vehicle, or tumor-bearing + glucocorticoid receptor antagonist groups. Circulating serum glucocorticoid and IL-6 levels were measured in addition to multiple body composition parameters, such as total body weight, lean body mass, and adipose content. The results of this study indicate a significant physiological alteration in the tumor-bearing host that causes severe and detrimental changes in body composition parameters. Regression analysis demonstrated a significant correlation between increased circulating glucocorticoid levels and alterations in body composition parameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the untoward effects of tumor-induced cachexia are not mediated primarily by the peripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.
癌症诱发的恶病质是恶性肿瘤患者中常见的一种表现。在患有恶病质的癌症患者中，已观察到循环糖皮质激素和白细胞介素-6（IL-6）水平升高，并且它们被认为是这一过程中的主要介质。本研究的目的是探讨循环糖皮质激素水平作为癌症诱发恶病质主要介质的作用。我们评估了使用受体拮抗剂RU-486抑制糖皮质激素是否能消除在一个特征明确的小鼠肿瘤诱发恶病质模型中所见的肌肉和脂肪组织的有害消耗。将小鼠（每组12只）随机分为对照组、荷瘤组、对照组+赋形剂组或荷瘤+糖皮质激素受体拮抗剂组。除了测量多个身体成分参数，如总体重、瘦体重和脂肪含量外，还检测了循环血清糖皮质激素和IL-6水平。本研究结果表明，荷瘤宿主存在显著的生理改变，导致身体成分参数发生严重且有害的变化。回归分析表明，循环糖皮质激素水平升高与身体成分参数改变之间存在显著相关性。给予糖皮质激素受体拮抗剂并不能消除这些观察到的缺陷。因此，我们得出结论，肿瘤诱发恶病质的不良影响并非主要由循环糖皮质激素水平升高的外周效应介导，而是可能涉及与IL-6的复杂相互作用。
