Role of interleukin-6 in cachexia: therapeutic implications.
Role of interleukin-6 in cachexia: therapeutic implications.
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DOI：
10.1097/spc.0000000000000091
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发表时间：
2014-12
影响因子：
2.1
通讯作者：
Carson JA
中科院分区：
文献类型：
--
作者：
Narsale AA;Carson JA
白介素6(IL-6)已成为参与某些癌症恶病质进展的细胞因子。这篇综述将介绍最近在动物模型和人类中有关将IL-6作为癌症恶病质治疗靶点的突破。IL-6可以靶向脂肪、骨骼肌、肠道和肝脏组织，这些都可以影响恶病质患者的康复。IL-6反式信号通过可溶性IL-6R在恶病质患者中具有放大IL-6信号的潜力。在骨骼肌中，慢性IL-6暴露诱导蛋白酶体和自噬蛋白降解途径，从而导致消耗。IL-6还与AMPK和NF-κB的激活间接相关。几个小鼠癌症模型已经清楚地证明，阻断IL-6及其相关信号可以减缓恶病质的进展。此外，针对IL-6和相关信号的药物可以缓解癌症患者的一些恶病质症状。对恶病质小鼠的研究表明，运动和营养治疗可以在恶病质进展过程中与慢性IL-6信号相互作用。IL-6仍然是一种很有前途的治疗策略，可以延缓多种癌症的恶病质进展。然而，改进这种治疗方法需要更好地了解IL-6的间接和直接作用，以及它在癌症患者中的组织特异性作用。
Interleukin-6 (IL-6) has emerged as a cytokine involved in cachexia progression with some cancers. This review will present recent breakthroughs in animal models and humans related to targeting IL-6 as a cancer cachexia therapy. IL-6 can target adipose, skeletal muscle, gut, and liver tissue, which can all affect cachectic patient recovery. IL-6 trans-signaling through the soluble IL-6r has the potential to amplify IL-6 signaling in the cachectic patient. In skeletal muscle chronic IL-6 exposure induces proteasome and autophagy protein degradation pathways that lead to wasting. IL-6 is also indirectly associated with AMPK and NF-κB activation. Several mouse cancer models have clearly demonstrated that blocking IL-6 and associated signaling can attenuate cachexia progression. Additionally, pharmaceuticals targeting IL-6 and associated signaling can relieve some cachectic symptoms in cancer patients. Research with cachectic mice has demonstrated that exercise and nutraceutical administration can interact with chronic IL-6 signaling during cachexia progression. IL-6 remains a promising therapeutic strategy for attenuating cachexia progression with many types of cancer. However, improvement of this treatment will require a better understanding of the indirect and direct effects of IL-6 as well as its tissue specific actions in the cancer patient.