St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and UNSW, Sydney, NSW, 2010, Australia.
J Cachexia Sarcopenia Muscle. 2012 Dec;3(4):239-43. doi: 10.1007/s13539-012-0082-6. Epub 2012 Aug 31.
Anorexia/cachexia is a common and currently mostly untreatable complication of advanced cancer. It is also a feature of a number of chronic diseases and can also occur as part of the normal ageing process. Over recent years, two different, but sometimes overlapping, processes have been identified to mediate anorexia/cachexia: those that act primarily on muscle reducing its mass and function, and processes that decrease nutrition leading to loss of both fat and muscle. In the case of at least some cancers, the latter process is sometimes driven by marked overexpression of macrophage inhibitory cytokine-1/growth differentiation factor 15 (MIC-1/GDF15). MIC-1/GDF15 is a transforming growth factor beta (TGF-β) family cytokine that is found in the serum of all normal individuals at an average concentration of about 0.6 ng/ml. Its increased expression in both cancers and other diseases can result in 10-100-fold or more elevation of its serum levels. In experimental animals, serum MIC-1/GDF15 levels at the lower end of this range induce anorexia by direct actions of the circulating cytokine on feeding centres in the brain. Mice with tumours overexpressing MIC-1/GDF15 display decreased food intake, loss of lean and fat mass and cachexia. That this process also mediates anorexia/cachexia in humans is suggested by the fact that there is a direct correlation between the degree of serum MIC-1/GDF15 elevation and the amount of cancer-related weight loss, the first such relationship demonstrated. Further, in experimental animals, weight loss can be reversed by neutralisation of tumour-produced MIC-1/GDF15 with a specific monoclonal antibody, suggesting the possibility of effective therapy of patients with the devastating complication of anorexia/cachexia.
厌食/恶病质是晚期癌症的一种常见且目前大多无法治疗的并发症。它也是许多慢性疾病的特征，也可能是正常衰老过程的一部分。近年来，已经确定了两种不同但有时重叠的过程来介导厌食/恶病质：主要作用于肌肉减少其质量和功能的过程，以及导致脂肪和肌肉减少的营养减少的过程。在至少某些癌症的情况下，后一种过程有时是由巨噬细胞抑制细胞因子-1/生长分化因子 15（MIC-1/GDF15）的明显过表达驱动的。MIC-1/GDF15 是一种转化生长因子β（TGF-β）家族细胞因子，在所有正常个体的血清中以约 0.6 ng/ml 的平均浓度存在。其在癌症和其他疾病中的表达增加可导致其血清水平升高 10-100 倍或更高。在实验动物中，血清 MIC-1/GDF15 水平处于该范围的较低端时，通过循环细胞因子对大脑中的摄食中心的直接作用引起厌食。过表达 MIC-1/GDF15 的肿瘤小鼠表现出摄食量减少、瘦体重和脂肪量减少以及恶病质。事实上，血清 MIC-1/GDF15 升高的程度与癌症相关体重减轻的量之间存在直接相关性，这表明该过程也介导了人类的厌食/恶病质，这表明了这种关系的首次证明。此外，在实验动物中，通过用特异性单克隆抗体中和肿瘤产生的 MIC-1/GDF15 可以逆转体重减轻，这表明对患有厌食/恶病质这种破坏性并发症的患者进行有效治疗的可能性。
