Functional and Morphological Improvement of Dystrophic Muscle by Interleukin 6 Receptor Blockade

Laura Pelosi, Maria Grazia Berardinelli, Loredana De Pasquale, Carmine Nicoletti, Adele D'Amico, Francesco Carvello, Gian Marco Moneta, Angela Catizone, Enrico Bertini, Fabrizio De Benedetti, Antonio Musarò

Research output: Contribution to journalArticle

Abstract

The anti-inflammatory agents glucocorticoids (GC) are the only available treatment for Duchenne muscular dystrophy (DMD). However, long-term GC treatment causes muscle atrophy and wasting. Thus, targeting specific mediator of inflammatory response may be more specific, more efficacious, and with fewer side effects. The pro-inflammatory cytokine interleukin (IL) 6 is overproduced in patients with DMD and in the muscle of mdx, the animal model for human DMD. We tested the ability of inhibition of IL6 activity, using an interleukin-6 receptor (Il6r) neutralizing antibody, to ameliorate the dystrophic phenotype. Blockade of endogenous Il6r conferred on dystrophic muscle resistance to degeneration and alleviated both morphological and functional consequences of the primary genetic defect. Pharmacological inhibition of IL6 activity leaded to changes in the dystrophic muscle environment, favoring anti-inflammatory responses and improvement in muscle repair. This resulted in a functional homeostatic maintenance of dystrophic muscle. These data provide an alternative pharmacological strategy for treatment of DMD and circumvent the major problems associated with conventional therapy.

Original languageEnglish
Pages (from-to)285-293
Number of pages9
JournalEBioMedicine
Volume2
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • IL6
  • Inflammation
  • Muscular dystrophy
  • Necrosis
  • Therapy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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  • Cite this

    Pelosi, L., Berardinelli, M. G., De Pasquale, L., Nicoletti, C., D'Amico, A., Carvello, F., Moneta, G. M., Catizone, A., Bertini, E., De Benedetti, F., & Musarò, A. (2015). Functional and Morphological Improvement of Dystrophic Muscle by Interleukin 6 Receptor Blockade. EBioMedicine, 2(4), 285-293. https://doi.org/10.1016/j.ebiom.2015.02.014