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Open Access Research article

IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse

Matthew C Kostek14*, Kanneboyina Nagaraju2, Emidio Pistilli23, Arpana Sali2, San-Huei Lai2, Brad Gordon1 and Yi-Wen Chen25*

Author Affiliations

1 Laboratory of Muscle and Translational Therapeutics, Department of Exercise Science, University of South Carolina, Columbia, SC, USA

2 Department of Integrative Systems Biology, George Washington University, Children’s National Medical Center, Washington, DC, USA

3 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

4 Laboratory of Muscle and Translational Therapeutics, 921 Assembly St. / PHRC / 3rd floor, Columbia, SC, USA

5 111 Michigan Ave. NW, Department of Integrative Systems Biology, George Washington University School of Medicine, Washington, DC, USA

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BMC Musculoskeletal Disorders 2012, 13:106  doi:10.1186/1471-2474-13-106

Published: 20 June 2012

Abstract

Background

IL-6 is a pleiotropic cytokine that modulates inflammatory responses and plays critical roles in muscle maintenance and remodeling. In the mouse model (mdx) of Duchenne Muscular Dystrophy, IL-6 and muscle inflammation are elevated, which is believed to contribute to the chronic inflammation and failure of muscle regeneration in DMD. The purpose of the current study was to examine the effect of blocking IL-6 signaling on the muscle phenotype including muscle weakness and pathology in the mdx mouse.

Methods

A monoclonal antibody against the IL-6 receptor (IL-6r mAb) that blocks local and systemic IL-6 signaling was administered to mdx and BL-10 mice for 5 weeks and muscle function, histology, and inflammation were examined.

Results

IL-6r mAb treatment increased mdx muscle inflammation including total inflammation score and ICAM-1 positive lumens in muscles. There was no significant improvement in muscle strength nor muscle pathology due to IL-6r mAb treatment in mdx mice.

Conclusions

These results showed that instead of reducing inflammation, IL-6 signaling blockade for 5 weeks caused an increase in muscle inflammation, with no significant change in indices related to muscle regeneration and muscle function. The results suggest a potential anti-inflammatory instead of the original hypothesized pro-inflammatory role of IL-6 signaling in the mdx mice.

Keywords:
IL-6; Muscular dystrophy; Inflammation; Duchenne