Combined XIL‐6R and urocortin‐2 treatment restores MDX diaphragm muscle force

• Published in: Muscle & nerve Vol. 56; no. 6; pp. E134 - E140
• Main Authors: Manning, Jennifer, Buckley, Maria M., O'Halloran, Ken D., O'Malley, Dervla
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2017
• Subjects: Animals; Antibodies; Autoantibodies - administration & dosage; Combined treatment; corticotrophin‐releasing factor; Corticotropin-Releasing Hormone - administration & dosage; Degeneration; Diaphragm; Diaphragm (anatomy); Diaphragm - drug effects; Diaphragm - physiology; Drug Therapy, Combination; Duchenne's muscular dystrophy; Dystrophin; Dystrophy; Generating capacity; Inflammation; Interleukin 6; Male; mdx; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; monoclonal; Muscle contraction; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscular dystrophy; Muscular Dystrophy, Animal - drug therapy; Muscular Dystrophy, Animal - physiopathology; Organ Culture Techniques; Random Allocation; Receptors, Interleukin-6 - administration & dosage; Rodents; Signaling; Treatment Outcome; Urocortin; urocortin 2; Urocortins - administration & dosage; Work capacity; mdx; corticotrophin-releasing factor; diaphragm; monoclonal; urocortin 2; interleukin-6
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.25644

ABSTRACT Introduction: Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration leading to immobility, respiratory failure, and premature death. As chronic inflammation and stress are implicated in DMD pathology, the efficacy of an anti‐inflammatory and anti‐stress intervention strategy in ameliorating diaphragm dysfunction was investigated. Methods: Diaphragm muscle contractile function was compared in wild‐type and dystrophin‐deficient mdx mice treated with saline, anti‐interleukin‐6 receptor antibodies (xIL‐6R), the corticotrophin‐releasing factor receptor 2 (CRFR2) agonist, urocortin 2, or both xIL‐6R and urocortin 2. Results: Combined treatment with xIL‐6R and urocortin 2 rescued impaired force in mdx diaphragms. Mechanical work production and muscle shortening was also improved by combined drug treatment. Discussion: Treatment which neutralizes peripheral IL‐6 signaling and stimulates CRFR2 recovers force‐generating capacity and the ability to perform mechanical work in mdx diaphragm muscle. These findings may be important in the search for therapeutic targets in DMD. Muscle Nerve 56: E134–E140, 2017