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

Sci Rep. 2017 Oct 11;7(1):12997. doi: 10.1038/s41598-017-13479-w.


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, rTNFα) 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-15rα in elderly myotubes confirmed that autocrine concentrations of IL-15 also support myogenesis. Co-incubation of differentiating myoblasts with rIL-15 and rTNFα, limited the reduction in MTT and nuclear fusion index (NFI) associated with rTNFα stimulation alone. IL-15rα neutralisation and rTNFα decreased MTT and NFI further. This, coupled with our observation that myotubes secrete IL-15 in response to TNFα 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging
  • Antibodies, Neutralizing / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Interleukin-15 / blood*
  • Male
  • Muscle Development / drug effects*
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology*
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / adverse effects*


  • Antibodies, Neutralizing
  • Interleukin-15
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha