title: Combined XIL-6R and urocortin-2 treatment restores MDX diaphragm muscle force.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Manning
authors.affiliation: Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Buckley
authors.affiliation: Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Ken D
authors.initials: KD
authors.lastname: O'Halloran
authors.affiliation: Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland.
authors.forename: Dervla
authors.identifier: http://orcid.org/0000-0002-7031-4879
authors.initials: D
authors.lastname: O'Malley
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage*; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000503:physiopathology; D009924:Organ Culture Techniques; D011897:Random Allocation; D019947:Receptors, Interleukin-6 / Q000008:administration & dosage*; D016896:Treatment Outcome; D054832:Urocortins / Q000008:administration & dosage*
chemical_list: D001323:Autoantibodies; D019947:Receptors, Interleukin-6; D054832:Urocortins; C518358:urocortin 2, mouse; D003346:Corticotropin-Releasing Hormone
keywords: corticotrophin-releasing factor; diaphragm; interleukin-6; mdx; monoclonal; urocortin 2