{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:14:48Z","timestamp":1791821688661,"version":"4.3.4"},"reference-count":215,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"BHF","doi-asserted-by":"publisher","award":["FS\/4yPhD\/F\/21\/34162"],"award-info":[{"award-number":["FS\/4yPhD\/F\/21\/34162"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"BHF","doi-asserted-by":"publisher","award":["SP\/F\/21\/150023"],"award-info":[{"award-number":["SP\/F\/21\/150023"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"BHF","doi-asserted-by":"publisher","award":["BB\/X017176\/1"],"award-info":[{"award-number":["BB\/X017176\/1"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BBSRC","award":["FS\/4yPhD\/F\/21\/34162"],"award-info":[{"award-number":["FS\/4yPhD\/F\/21\/34162"]}]},{"name":"BBSRC","award":["SP\/F\/21\/150023"],"award-info":[{"award-number":["SP\/F\/21\/150023"]}]},{"name":"BBSRC","award":["BB\/X017176\/1"],"award-info":[{"award-number":["BB\/X017176\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Interleukin-6 (IL-6) is a pleiotropic cytokine with critical roles in immune regulation, inflammation, and haematopoiesis. While its functions in host defence and tissue repair are well established, accumulating evidence suggests that IL-6 also can directly and indirectly modulate megakaryocyte and platelet biology. This review examines the mechanistic basis supporting IL-6-mediated platelet hyper-responsiveness, in addition to its effect on megakaryopoiesis and thrombopoiesis in thromboinflammatory disease states. We discuss how IL-6-mediated trans-signalling may sensitizes platelets to activation, and that this may be exclusive to glycoprotein VI (GPVI) stimulation due to Janus kinase (JAK)\u2013signal transducer 2 crosstalk, in addition to other mechanisms that may contribute to priming platelets. We further highlight clinical evidence linking IL-6 to thrombotic complications in cardiovascular disease and infection (e.g., COVID-19 and sepsis). Given the emerging interest in IL-6-targeting therapies as anti-inflammatory and anti-thrombotic agents, a thorough understanding of how IL-6 can drive platelet responsiveness is crucial.<\/jats:p>","DOI":"10.3390\/cells14110766","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T12:15:43Z","timestamp":1747916143000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["IL-6 as a Mediator of Platelet Hyper-Responsiveness"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-0280","authenticated-orcid":false,"given":"Connor Elliot","family":"Webb","sequence":"first","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Vautrinot","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6467-5715","authenticated-orcid":false,"given":"Ingeborg","family":"Hers","sequence":"additional","affiliation":[{"name":"School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/qjmed\/os-24.95.285","article-title":"The Blood-Platelet: Its Clinical Significance","volume":"os-24","author":"MacKay","year":"1931","journal-title":"QJM Int. 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