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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Anorexia/cachexia of chronic diseases: a role for the TGF‐β family cytokine MIC‐1/GDF15
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Anorexia/cachexia of chronic diseases: a role for the TGF‐β family cytokine MIC‐1/GDF15

机译：慢性疾病的厌食/恶病质：TGF-β家族细胞因子MIC-1 / GDF15的作用

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AbstractAnorexia/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.
机译：摘要厌食/恶病质是一种常见的且目前几乎无法治愈的晚期癌症并发症。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的，但有时是重叠的过程来介导厌食/恶病质：主要作用于肌肉以减少其质量和功能的过程，以及减少营养以导致脂肪和肌肉损失的过程。在至少某些癌症的情况下，后一过程有时是由巨噬细胞抑制性细胞因子-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均以约0.6 ng / ml的平均浓度存在。它在癌症和其他疾病中的表达增加可能导致其血清水平升高10-100倍或更多。在实验动物中，此范围下端的血清MIC-1 / GDF15水平通过循环细胞因子对大脑进食中心的直接作用而引起厌食。 MIC-1 / GDF15过度表达的小鼠表现出食物摄入减少，瘦肉和脂肪减少以及恶病质。血清MIC-1 / GDF15升高的程度与癌症相关的体重减轻量之间存在直接相关性这一事实表明，该过程还介导了人类的厌食/恶病质，这是第一个这样的关系。此外，在实验动物中，可以通过用特异性单克隆抗体中和肿瘤产生的MIC-1 / GDF15来逆转体重减轻，这表明有效治疗患有严重厌食/恶病质并发症的患者的可能性。

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