Peer-Reviewed Journal Details
Mandatory Fields
Manning J, Buckley MM, O'Halloran KD, O'Malley D
Muscle & Nerve
Combined xIL-6R and urocortin-2 treatment restores mdx diaphragm muscle force
WOS: 6 ()
Optional Fields
Corticotrophin-releasing factor Diaphragm Interleukin-6 mdx Monoclonal Urocortin 2
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. 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.
Grant Details