IL-6 as a Mediator of Platelet Hyper-Responsiveness

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...

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Main Authors: Connor Elliot Webb, Jordan Vautrinot, Ingeborg Hers
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/11/766
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author Connor Elliot Webb
Jordan Vautrinot
Ingeborg Hers
author_facet Connor Elliot Webb
Jordan Vautrinot
Ingeborg Hers
author_sort Connor Elliot Webb
collection DOAJ
description 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)–signal 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.
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spelling doaj-art-1e4f4997f3a7431aa9e822ca0ca4b82b2025-08-20T03:11:22ZengMDPI AGCells2073-44092025-05-01141176610.3390/cells14110766IL-6 as a Mediator of Platelet Hyper-ResponsivenessConnor Elliot Webb0Jordan Vautrinot1Ingeborg Hers2School of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UKSchool of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UKSchool of Physiology, Pharmacology and Neuroscience, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UKInterleukin-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)–signal 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.https://www.mdpi.com/2073-4409/14/11/766interleukin-6plateletshyper-responsivenessthrombo-inflammationthrombosis
spellingShingle Connor Elliot Webb
Jordan Vautrinot
Ingeborg Hers
IL-6 as a Mediator of Platelet Hyper-Responsiveness
Cells
interleukin-6
platelets
hyper-responsiveness
thrombo-inflammation
thrombosis
title IL-6 as a Mediator of Platelet Hyper-Responsiveness
title_full IL-6 as a Mediator of Platelet Hyper-Responsiveness
title_fullStr IL-6 as a Mediator of Platelet Hyper-Responsiveness
title_full_unstemmed IL-6 as a Mediator of Platelet Hyper-Responsiveness
title_short IL-6 as a Mediator of Platelet Hyper-Responsiveness
title_sort il 6 as a mediator of platelet hyper responsiveness
topic interleukin-6
platelets
hyper-responsiveness
thrombo-inflammation
thrombosis
url https://www.mdpi.com/2073-4409/14/11/766
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