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Scandinavian Med Sci Sports - 2022 - Nash - IL‐6 signaling in acute exercise and chronic training Potential consequences.pdf (640.82 kB)

IL-6 signaling in acute exercise and chronic training: Potential consequences for health and athletic performance

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journal contribution
posted on 2022-10-14, 09:23 authored by Dan Nash, Michael G Hughes, Lee ButcherLee Butcher, Rebecca Aicheler, Paul M. Smith

 The cytokine interleukin-6 (IL-6) is involved in a diverse set of physiological processes. Traditionally, IL-6 has been thought of in terms of its inflammatory actions during the acute phase response and in chronic conditions such as rheumatoid arthritis and obesity. However, IL-6 is also an important signaling molecule during exercise, being acutely released from working muscle fibers with increased exercise duration, intensity, and muscle glycogen depletion. In this context, IL-6 enables muscle-organ crosstalk, facilitating a coordinated response to help maintain muscle energy homeostasis, while also having anti-inflammatory actions. The range of actions of IL-6 can be explained by its dichotomous signaling pathways. Classical signaling involves IL-6 binding to a cell-surface receptor (mbIL-6R; present on only a small number of cell types) and is the predominant signaling mechanism during exercise. Trans-signaling involves IL-6 binding to a soluble version of its receptor (sIL-6R), with the resulting complex having a much greater half-life and the ability to signal in all cell types. Trans-signaling drives the inflammatory actions of IL-6 and is the predominant pathway in disease. A single nucleotide polymorphism (rs2228145) on the IL-6R gene can modify the classical/trans-signaling balance through increasing the levels of sIL-6R. This SNP has clinical significance, having been linked to inflammatory conditions such as rheumatoid arthritis and type 1 diabetes, as well as to the severity of symptoms experienced with COVID-19. This review will describe how acute exercise, chronic training and the rs2228145 SNP can modify the IL-6 signaling pathway and the consequent implications for health and athletic performance. 


European Social Fund


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Scandinavian Journal of Medicine and Science in Sports




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Nash, D., Hughes, M.G., Butcher, L., Aicheler, R., Smith, P., Cullen, T. and Webb, R. (2022) 'IL‐6 signalling in acute exercise and chronic training: potential consequences for health and athletic performance', Scandinavian Journal of Medicine & Science in Sports. DOI: 10.1111/sms.14241

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Cardiff Met Affiliation

  • Cardiff School of Sport and Health Sciences

Cardiff Met Authors

Dan Nash Michael G. Hughes Lee Butcher Rebecca Aicheler Paul Smith Richard Webb

Cardiff Met Research Centre/Group

  • Public Health and Wellbeing

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  • © The Authors


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