Increased levels of interleukin-6 exacerbate the dystrophic phenotype in mdx mice
Pelosi L, Berardinelli MG, Forcina L, Spelta E, Rizzuto E, Nicoletti C, Camilli C, Testa E, Catizone A, De Benedetti F, MusarĂ² A, ASI sponsor
Aug - 2015
DOI: 10.1093/hmg/ddv323
ISSN : 1460-2083 ;
journal : Human Molecular Genetics

Volume : 24 ; Issue : 21
type: Article Journal

Duchenne muscular dystrophy (DMD) is characterized by progressive lethal muscle degeneration and chronic inflammatory response. The mdx mouse strain has served as the animal model for human DMD. However, while DMD patients undergo extensive necrosis, the affected muscles of adult mdx mice rapidly regenerates and regains structural and functional integrity. The basis for the mild effects observed in mice compared with the lethal consequences in humans remains unknown. In this study, we provide evidence that interleukin-6 (IL-6) is causally linked to the pathogenesis of muscular dystrophy. We report that forced expression of IL-6, in the adult mdx mice, recapitulates the severe phenotypic characteristics of DMD in humans. Increased levels of IL-6 exacerbate the dystrophic muscle phenotype, sustaining inflammatory response and repeated cycles of muscle degeneration and regeneration, leading to exhaustion of satellite cells. The mdx/IL6 mouse closely approximates the human disease and more faithfully recapitulates the disease progression in humans. This study promises to significantly advance our understanding of the pathogenic mechanisms that lead to DMD.

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Notes : This work was supported by Telethon (grant no. GGP13013) and partly by Agenzia Spaziale Italiana (grant no. 2013-088-RO)