AUTHOR=Thome Jason G. , Reeder Evan L. , Collins Sean M. , Gopalan Poornima , Robson Matthew J. TITLE=Contributions of Interleukin-1 Receptor Signaling in Traumatic Brain Injury JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=13 YEAR=2020 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2019.00287 DOI=10.3389/fnbeh.2019.00287 ISSN=1662-5153 ABSTRACT=

Traumatic brain injury (TBI) in various forms affects millions in the United States annually. There are currently no FDA-approved therapies for acute injury or the chronic comorbidities associated with TBI. Acute phases of TBI are characterized by profound neuroinflammation, a process that stimulates the generation and release of proinflammatory cytokines including interleukin-1α (IL-1α) and IL-1β. Both forms of IL-1 initiate signaling by binding with IL-1 receptor type 1 (IL-1R1), a receptor with a natural, endogenous antagonist dubbed IL-1 receptor antagonist (IL-1Ra). The recombinant form of IL-1Ra has gained FDA approval for inflammatory conditions such as rheumatoid arthritis, prompting interest in repurposing these pharmacotherapies for other inflammatory diseases/injury states including TBI. This review summarizes the currently available preclinical and clinical literature regarding the therapeutic potential of inhibiting IL-1-mediated signaling in the context of TBI. Additionally, we propose specific research areas that would provide a greater understanding of the role of IL-1 signaling in TBI and how these data may be beneficial for the development of IL-1-targeted therapies, ushering in the first FDA-approved pharmacotherapy for acute TBI.