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

BMC Musculoskeletal Disorders

Yi-Wen Chen³  Brad Gordon¹  San-Huei Lai⁴  Arpana Sali⁴  Emidio Pistilli²  Kanneboyina Nagaraju⁴  Matthew C Kostek⁵ 

[1] Laboratory of Muscle and Translational Therapeutics, Department of Exercise Science, University of South Carolina, Columbia, SC, USA;University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA;111 Michigan Ave. NW, Department of Integrative Systems Biology, George Washington University School of Medicine, Washington, DC, USA;Department of Integrative Systems Biology, George Washington University, Children’s National Medical Center, Washington, DC, USA;Laboratory of Muscle and Translational Therapeutics, 921 Assembly St. / PHRC / 3rd floor, Columbia, SC, USA

关键词: Duchenne;    Inflammation;    Muscular dystrophy;    IL-6;   

Others  :  1149413
DOI  :  10.1186/1471-2474-13-106

 received in 2011-10-18, accepted in 2012-05-24,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Kostek et al.; licensee BioMed Central Ltd.

【 图 表 】

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