Interleukin-15 administration improves diaphragm muscle pathology and function in dystrophic mdx mice.
Interleukin (IL)-15, a cytokine expressed in skeletal muscle, has been shown to have muscle anabolic effects in vitro and to slow muscle wasting in rats with cancer cachexia. Whether IL-15 has therapeutic potential for diseases such as Duchenne muscular dystrophy (DMD) is unknown. We examined whether IL-15 administration could ameliorate the dystrophic pathology in the diaphragm muscle of the mdx mouse, an animal model for DMD. Four weeks of IL-15 treatment improved diaphragm strength, a highly significant finding because respiratory function is a mortality predictor in DMD. Enhanced diaphragm function was associated with increased muscle fiber cross-sectional area and decreased collagen infiltration. IL-15 administration was not associated with changes in T-cell populations or alterations in specific components of the ubiquitin proteasome pathway. To determine the effects of IL-15 on myofiber regeneration, muscles of IL-15-treated and untreated wild-type mice were injured myotoxically, and their functional recovery was assessed. IL-15 had a mild anabolic effect, increasing fiber cross-sectional area after 2 and 6 days but not after 10 days. Our findings demonstrate that IL-15 administration improves the pathophysiology of dystrophic muscle and highlight a possible therapeutic role for IL-15 in the treatment of neuromuscular disorders especially in which muscle wasting is indicated.
Harcourt
Leah J
LJ
Department of Physiology, University of Melbourne, Victoria, Australia, 3010.
Holmes
Anna Greer
AG
Gregorevic
Paul
P
Schertzer
Jonathan D
JD
Stupka
Nicole
N
Plant
David R
DR
Lynch
Gordon S
GS
D000818:Animals; D003964:Diaphragm / Q000187:drug effects* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019409:Interleukin-15 / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy*; D012038:Regeneration / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
D019409:Interleukin-15; D025801:Ubiquitin; D044763:Ubiquitin-Conjugating Enzymes