title: Functional and Morphological Improvement of Dystrophic Muscle by Interleukin 6 Receptor Blockade.
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.
authors.affiliation: Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, 00161, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pelosi
authors.affiliation: Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, 00161, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Berardinelli
authors.affiliation: Division of Rheumatology, Bambino Gesù Children's Hospital, Rome 00100, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: De Pasquale
authors.affiliation: Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, 00161, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Nicoletti
authors.affiliation: Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Disease, Bambino Gesù Children's Hospital, Rome 00100, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: D'Amico
authors.affiliation: Division of Rheumatology, Bambino Gesù Children's Hospital, Rome 00100, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Carvello
authors.affiliation: Division of Rheumatology, Bambino Gesù Children's Hospital, Rome 00100, Italy.
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Moneta
authors.affiliation: Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, 00161, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Catizone
authors.affiliation: Department of Neuroscience, Unit of Neuromuscular and Neurodegenerative Disease, Bambino Gesù Children's Hospital, Rome 00100, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.affiliation: Division of Rheumatology, Bambino Gesù Children's Hospital, Rome 00100, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: De Benedetti
authors.affiliation: Institute Pasteur-Cenci Bolognetti, DAHFMO-Unit of Histology and Medical Embryology, IIM, Sapienza University of Rome, 00161, Italy ; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Rome 00161, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Musarò
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006706:Homeostasis; D007249:Inflammation / Q000150:complications / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009132:Muscles / Q000473:pathology* / Q000503:physiopathology*; D009137:Muscular Dystrophy, Animal / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000097:blood / Q000473:pathology* / Q000503:physiopathology*; D009336:Necrosis; D010641:Phenotype; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D019947:Receptors, Interleukin-6
keywords: IL6; Inflammation; Muscular dystrophy; Necrosis; Therapy