Basic Science Research
Combined XIL-6R and urocortin-2 treatment restores MDX diaphragm muscle force
Jennifer Manning BSc, PhD,
Maria M. Buckley BSc, PhD,
Ken D. O'Halloran BSc, PhD,
Dervla O'Malley BSc, PhD,
Jennifer Manning BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Search for more papers by this authorMaria M. Buckley BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Search for more papers by this authorKen D. O'Halloran BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Search for more papers by this authorCorresponding Author
Dervla O'Malley BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Correspondence to: D. O'Malley; [email protected]Search for more papers by this authorJennifer Manning BSc, PhD,
Maria M. Buckley BSc, PhD,
Ken D. O'Halloran BSc, PhD,
Dervla O'Malley BSc, PhD,
Jennifer Manning BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Search for more papers by this authorMaria M. Buckley BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Search for more papers by this authorKen D. O'Halloran BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Search for more papers by this authorCorresponding Author
Dervla O'Malley BSc, PhD
Department of Physiology, Western Gateway Building, University College Cork, Cork, Ireland
Correspondence to: D. O'Malley; [email protected]Search for more papers by this authorFunding: J.M. was supported by funding from Muscular Dystrophy Ireland and the Department of Physiology, UCC. The monoclonal anti-IL-6 receptor antibody was gifted by Chugai Pharmaceuticals, Tokyo, Japan.
Conflicts of Interest: None of the authors has any conflict of interest to disclose.
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
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