@article {NewellENEURO.0385-17.2018, author = {Elizabeth A. Newell and Brittany P. Todd and Jolonda Mahoney and Andrew A. Pieper and Polly J. Ferguson and Alexander G. Bassuk}, title = {Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury}, volume = {5}, number = {2}, elocation-id = {ENEURO.0385-17.2018}, year = {2018}, doi = {10.1523/ENEURO.0385-17.2018}, publisher = {Society for Neuroscience}, abstract = {Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion{\textendash}mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling.}, URL = {https://www.eneuro.org/content/5/2/ENEURO.0385-17.2018}, eprint = {https://www.eneuro.org/content/5/2/ENEURO.0385-17.2018.full.pdf}, journal = {eNeuro} }