Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury

Journal of Neuroinflammation

Michael G Fehlings¹  Donald R Branch²  Kajana Satkunendrarajah³  Dung H Nguyen³  Newton Cho³ 

[1] Krembil Chair in Neural Repair and Regeneration, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada;Research and Development, Canadian Blood Services, Departments of Medicine and Laboratory Medicine and Pathobiology, Division of Cell and Molecular Biology, Toronto General Research Institute, University of Toronto, 67 College Street, Toronto, ON, M5G 2M1, Canada;Department of Genetics and Development, Toronto Western Research Institute and Spinal Program, Krembil Neuroscience Center, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada

关键词: electrophysiology;    immune response;    gp130 receptor;    locomotor recovery;    mouse model;    IL-11;    Spinal cord injury;   

Others  :  1212509
DOI  :  10.1186/1742-2094-9-134

 received in 2012-01-31, accepted in 2012-05-16,  发布年份 2012

【 摘 要 】

Background

Spinal cord injury (SCI) is a devastating condition with substantial functional and social morbidity. Previous research has established that the neuroinflammatory response plays a significant role in cord damage post-SCI. However, global immunosuppressive therapies have demonstrated mixed results. As a result, more specific therapies modulating inflammation after injury are needed. In this regard, research into cytokine signaling has demonstrated that cytokines of the gp130 family including IL-6 and leukemia inhibitory factor (LIF) play key roles in mediating damage to the spinal cord. Since members of the gp130 family all share a common signal transduction pathway via the JAK/STAT system, we performed the first study of a relatively new member of the gp130 family, IL-11, in SCI.

Methods

A validated clip-compression mouse model of SCI was used to assess for temporal changes in expression of IL-11 and its receptor, IL-11Rα, post-SCI. To elucidate the role of IL-II in the pathophysiology of SCI, we compared differences in locomotor recovery (Basso Mouse Score; CatWalk), electrophysiological spinal cord signaling, histopathology, and the acute inflammatory neutrophil response in IL-11Rα knockouts with littermate wild-type C57BL/6 mice.

Results

We found an increase in gene expression of IL-11 in the spinal cord to a peak at twenty-four hours post-SCI with increases in IL-11Rα gene expression, peaking at seven days post-SCI. In spite of clear changes in the temporal expression of both IL-11 and its receptor, we found that there were no significant differences in motor function, electrophysiological signaling, histopathology, or neutrophil infiltration into the spinal cord between wild-type and knockout mice.

Conclusions

This is the first study to address IL-11 in SCI. This study provides evidence that IL-11 signaling may not play as significant a role in SCI as other gp130 cytokines, which will ideally guide future therapy design and the signaling pathways those therapies target.

【 授权许可】

   
2012 Cho et al.; licensee BioMed Central Ltd.

【 图 表 】

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