title: Role of interleukin-6 in cachexia: therapeutic implications.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Aditi A
authors.initials: AA
authors.lastname: Narsale
authors.forename: James A
authors.initials: JA
authors.lastname: Carson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D001343:Autophagy; D002100:Cachexia / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D007421:Intestine, Small / Q000378:metabolism; D053612:Janus Kinases / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000378:metabolism; D009369:Neoplasms / Q000150:complications*; D059748:Proteolysis; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D053612:Janus Kinases