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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2012

Open Access 01-12-2012 | Research article

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

Authors: Matthew C Kostek, Kanneboyina Nagaraju, Emidio Pistilli, Arpana Sali, San-Huei Lai, Brad Gordon, Yi-Wen Chen

Published in: BMC Musculoskeletal Disorders | Issue 1/2012

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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.
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Metadata
Title
IL-6 signaling blockade increases inflammation but does not affect muscle function in the mdx mouse
Authors
Matthew C Kostek
Kanneboyina Nagaraju
Emidio Pistilli
Arpana Sali
San-Huei Lai
Brad Gordon
Yi-Wen Chen
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2012
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-13-106

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