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Role of interleukin-6 in cachexia: therapeutic implications

Narsale, Aditi A.a,b; Carson, James A.a,b,c

Current Opinion in Supportive and Palliative Care: December 2014 - Volume 8 - Issue 4 - p 321–327
doi: 10.1097/SPC.0000000000000091
CACHEXIA, NUTRITION AND HYDRATION: Edited by Aminah Jatoi and Florian Strasser

Purpose of review Interleukin-6 (IL-6) has emerged as a cytokine involved in cachexia progression with some cancers. This review will present the recent breakthroughs in animal models and humans related to targeting IL-6 as a cancer cachexia therapy.

Recent findings 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 the skeletal muscle, chronic IL-6 exposure induces proteasome and autophagy protein degradation pathways that lead to wasting. IL-6 is also indirectly associated with AMP-activated kinase (AMPK) and nuclear factor kappa B (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.

Summary 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.

aIntegrative Muscle Biology Laboratory, Department of Exercise Science

bDivision of Applied Physiology, Department of Exercise Science

cCenter for Colon Cancer Research, University of South Carolina, Columbia, South Carolina, USA

Correspondence to James A. Carson, PhD, Department of Exercise Science, Public Health Research Center, University of South Carolina, Room 405, 921 Assembly Street, Columbia, SC 29208, USA. Tel: +1 803 777 0809, +1 803 777 0142; fax: +1 803 777 8422; e-mail:

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