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Current treatments are limited and do not target the profound immune response associated with injury. This immune response reflects a convergence of peripheral and central nervous system\u2013resident immune cells whose interaction is mediated in part by a disruption in the blood\u2013brain barrier (BBB). The diverse family of cytokines helps to govern this communication and among these, Interleukin (IL)-6 is a notable player in the immune response to acute neurological injury. It is also a well-established pharmacological target in a variety of other disease contexts. In TBI, elevated IL-6 levels are associated with worse outcomes, but the role of IL-6 in response to injury is double-edged. IL-6 promotes neurogenesis and wound healing in animal models of TBI, but it may also contribute to disruptions in the BBB and the progression of cerebral edema. Here, we review IL-6 biology in the context of TBI, with an eye to clarifying its controversial role and understanding its potential as a target for modulating the immune response in this disease.<\/jats:p>","DOI":"10.1089\/neu.2023.0135","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T10:12:14Z","timestamp":1683799934000},"page":"2249-2269","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":55,"title":["Interleukin-6 in Traumatic Brain Injury: A Janus-Faced Player in Damage and Repair"],"prefix":"10.1177","volume":"40","author":[{"given":"Prajwal","family":"Ciryam","sequence":"first","affiliation":[{"name":"Shock Trauma Neurocritical Care, Program in Trauma, R Adams Cowley Shock Trauma Center, University of Maryland Medical System, Baltimore, Maryland, USA."},{"name":"Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Gerzanich","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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