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IL-15 promotes human myogenesis and mitigates the detrimental effects of TNF? on myotube development


Mary F.

Graham R. Wallace

Simon W. Jones


Studies in murine cell lines and in mouse models suggest that IL-15 promotes myogenesis and may protect against the inflammation-mediated skeletal muscle atrophy which occurs in sarcopenia and cachexia. The effects of IL-15 on human skeletal muscle growth and development remain largely uncharacterised. Myogenic cultures were isolated from the skeletal muscle of young and elderly subjects. Myoblasts were differentiated for 8 d, with or without the addition of recombinant cytokines (rIL-15, rTNF?) and an IL-15 receptor neutralising antibody. Although myotubes were 19% thinner in cultures derived from elderly subjects, rIL-15 increased the thickness of myotubes (MTT) from both age groups to a similar extent. Neutralisation of the high-affinity IL-15 receptor binding subunit, IL-15r? in elderly myotubes confirmed that autocrine concentrations of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with rIL-15 and rTNF?, limited the reduction in MTT and nuclear fusion index (NFI) associated with rTNF? stimulation alone. IL-15r? neutralisation and rTNF? decreased MTT and NFI further. This, coupled with our observation that myotubes secrete IL-15 in response to TNF? stimulation supports the notion that IL-15 serves to mitigate inflammatory skeletal muscle loss. IL-15 may be an effective therapeutic target for the attenuation of inflammation-mediated skeletal muscle atrophy.


O’Leary, M. F., Wallace, G. R., Bennett, A. J., Tsintzas, K., & Jones, S. W. (in press). IL-15 promotes human myogenesis and mitigates the detrimental effects of TNFα on myotube development. Scientific Reports, 7(1), Article 12997.

Journal Article Type Article
Acceptance Date Sep 26, 2017
Online Publication Date Oct 11, 2017
Deposit Date Apr 5, 2018
Publicly Available Date Apr 5, 2018
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
Article Number 12997
Keywords Ageing; Muscle stem cells
Public URL
Publisher URL


s41598-017-13479-w.pdf (4.7 Mb)

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