Glucocorticoid blockade does not abrogate tumor-induced cachexia

Cancer-induced cachexia is a common manifestation observed in patients with malignancies. Elevated levels of circulating,glucocorticoids and interleuk in-6 (IL-6) hare been observed in cancer patients with cachexia and are imp licated as major mediators in this process. The purpose of this study was t o investigate the role of circulating glucocorticoid levels as primary medi ators in cancer-induced cachexia. We evaluated whether inhibition of glucoc orticoids with the receptor antagonist RU-486 could abrogate the detrimenta l 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 recepto r 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 increase d circulating glucocorticoid levels and alterations in body composition par ameters. These observed defects were not abrogated with the administration of a glucocorticoid receptor antagonist. We therefore conclude that the unt oward effects of tumor-induced cachexia are not mediated primarily by the p eripheral effects of high circulating glucocorticoid levels but may involve a complex interaction with IL-6.