Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury
1 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
2 Department of Surgery, University of Toronto, 100 College Street, Toronto, ON, M5G 1L5, Canada
3 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
4 Krembil Chair in Neural Repair and Regeneration, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada
Journal of Neuroinflammation 2012, 9:134 doi:10.1186/1742-2094-9-134Published: 20 June 2012
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.
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.
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.
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.