Combined xIL-6R and urocortin-2 treatment restores mdx diaphragm muscle force

Thumbnail Image
Files
2732.pdf(1.11 MB)
Accepted Version
Date
2017-05-29
Authors
Manning, Jennifer
Buckley, Maria M.
O'Halloran, Ken D.
O'Malley, Dervla
Journal Title
Journal ISSN
Volume Title
Publisher
John Wiley & Sons, Inc.
Published Version
10.1002/mus.25644
Research Projects
Organizational Units
Journal Issue
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. 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.
Description
Keywords
Corticotrophin-releasing factor , Diaphragm , Interleukin-6 , mdx , Monoclonal , Urocortin 2
Citation
Manning, J., Buckley, M. M., O'Halloran, K. D. and O'Malley, D. (2017) 'Combined xIL-6R and urocortin-2 treatment restores mdx diaphragm muscle force', Muscle and Nerve. doi:10.1002/mus.25644
Link to publisher’s version
URI
https://hdl.handle.net/10468/4521
Collections
Physiology - Journal Articles
Copyright
© 2017, Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Manning, J., Buckley, M. M., O'Halloran, K. D. and O'Malley, D. (2017) 'Combined xIL-6R and urocortin-2 treatment restores mdx diaphragm muscle force', Muscle and Nerve, which has been published in final form at http://dx.doi.org/10.1002/mus.25644. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.