PT - JOURNAL ARTICLE AU - Elizabeth A. Newell AU - Brittany P. Todd AU - Jolonda Mahoney AU - Andrew A. Pieper AU - Polly J. Ferguson AU - Alexander G. Bassuk TI - Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury AID - 10.1523/ENEURO.0385-17.2018 DP - 2018 Mar 01 TA - eneuro PG - ENEURO.0385-17.2018 VI - 5 IP - 2 4099 - http://www.eneuro.org/content/5/2/ENEURO.0385-17.2018.short 4100 - http://www.eneuro.org/content/5/2/ENEURO.0385-17.2018.full SO - eNeuro2018 Mar 01; 5 AB - 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–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.