Hyperacute Interleukin ‐1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion
12 affiliations
- 1Department of Neurology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 2Department of Neuroradiology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 3Institute of Clinical Chemistry and Laboratory Medicine University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 4Institute of Systems Immunology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 5Department of Immunology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 6Bioinformatics Core University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 7Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 8Department of Neurobiology Research, Institute of Molecular Medicine University of Southern Denmark Odense Denmark
- 9Department of Neuroscience University of Kentucky Lexington KY USA
- 10Hamburg Center for Translational Immunology University Medical Center Hamburg‐Eppendorf Hamburg Germany
- 11Centre for Cardiovascular Biology and Disease Research La Trobe University Melbourne VIC Australia
- 12Institute of Neuropathology University Medical Center Hamburg‐Eppendorf Hamburg Germany
Abstract
OBJECTIVE: Cerebral ischemia remains a major cause of disability, and the contribution of the hyperacute immune response is increasingly recognized. The aim of this study was to investigate the local inflammatory response in the affected brain of stroke patients with large vessel occlusion during the hyperacute phase of stroke. METHODS: To decipher the role of myeloid immune cells in stroke-induced inflammation, we performed an unsupervised multiomics analysis of innate immune pathways in ischemic blood obtained directly from the occluded middle cerebral artery in 54 patients undergoing mechanical recanalization. Paired nonischemic arterial blood served as an internal control. RESULTS: Stroke triggered a local hyperacute activation of classical monocytes and neutrophils in the ischemic cerebral vasculature, with interleukin (IL)-1β emerging as a key mediator of inflammation. Elevated plasma adenosine triphosphate levels and inflammasome priming in intravascular monocytes were associated with IL-1β production within the occluded middle cerebral artery within 4.5 hours of stroke onset. IL-1β release coincided with increased neutrophil-attracting chemokines (C-X-C motif chemokine ligand 1 [CXCL1], IL-8). Locally activated neutrophils formed neutrophil extracellular traps (NETs) within the ischemic vasculature, a hallmark of thromboinflammation. Postmortem analyses revealed NET deposition within ischemic brain parenchyma. INTERPRETATION: These findings indicate increased IL-1β expression and enhanced NET formation within the cerebral circulation in stroke caused by large vessel occlusion, suggesting that these mechanisms might contribute to early stroke pathophysiology and represent potential targets for immunomodulatory strategies. ANN NEUROL 2026;100:824-840.
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BibTeX
@article{munsterberg2026hyperacute,
title = {{Hyperacute Interleukin ‐1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion}},
author = {Justine Münsterberg and Caspar Brekenfeld and Hanna Englert and Marius Piepke and Regine J. Dress and Martin Oertel and Tina Fischer and Romy Hackbusch and Mingming Zha and Haodi Cai and Christian Casar and Ines Sophie Schädlich and Leo Winter and Alina Jander and Karoline Degenhardt and Maxim Bester and Fabian Flottmann and Uta Meta Paula Hanning and Brigitte Holst and Anna Worthmann and Johanna Hiefner and Berenike Rutz and Eckhard Schlemm and Götz Thomalla and Bettina Hjelm Clausen and Ann Marie Stowe and Immo Prinz and Thiruma Valavan Arumugam and Markus Glatzel and Thomas Renné and Jens Fiehler and Eva Tolosa and Tim Magnus and Mathias Gelderblom},
journal = {Annals of Neurology},
year = {2026},
month = jun,
doi = {10.1002/ana.78284},
url = {https://doi.org/10.1002/ana.78284},
note = {CC BY},
}
RIS
TY - JOUR
TI - Hyperacute Interleukin ‐1β Production and Neutrophil Extracellular Trap Formation in the Cerebral Circulation of Stroke Patients with Large Vessel Occlusion
AU - Justine Münsterberg
AU - Caspar Brekenfeld
AU - Hanna Englert
AU - Marius Piepke
AU - Regine J. Dress
AU - Martin Oertel
AU - Tina Fischer
AU - Romy Hackbusch
AU - Mingming Zha
AU - Haodi Cai
AU - Christian Casar
AU - Ines Sophie Schädlich
AU - Leo Winter
AU - Alina Jander
AU - Karoline Degenhardt
AU - Maxim Bester
AU - Fabian Flottmann
AU - Uta Meta Paula Hanning
AU - Brigitte Holst
AU - Anna Worthmann
AU - Johanna Hiefner
AU - Berenike Rutz
AU - Eckhard Schlemm
AU - Götz Thomalla
AU - Bettina Hjelm Clausen
AU - Ann Marie Stowe
AU - Immo Prinz
AU - Thiruma Valavan Arumugam
AU - Markus Glatzel
AU - Thomas Renné
AU - Jens Fiehler
AU - Eva Tolosa
AU - Tim Magnus
AU - Mathias Gelderblom
PY - 2026
DA - 2026/06/22
JO - Annals of Neurology
DO - 10.1002/ana.78284
UR - https://doi.org/10.1002/ana.78284
AB - OBJECTIVE: Cerebral ischemia remains a major cause of disability, and the contribution of the hyperacute immune response is increasingly recognized. The aim of this study was to investigate the local inflammatory response in the affected brain of stroke patients with large vessel occlusion during the hyperacute phase of stroke. METHODS: To decipher the role of myeloid immune cells in stroke-induced inflammation, we performed an unsupervised multiomics analysis of innate immune pathways in ischemic blood obtained directly from the occluded middle cerebral artery in 54 patients undergoing mechanical recanalization. Paired nonischemic arterial blood served as an internal control. RESULTS: Stroke triggered a local hyperacute activation of classical monocytes and neutrophils in the ischemic cerebral vasculature, with interleukin (IL)-1β emerging as a key mediator of inflammation. Elevated plasma adenosine triphosphate levels and inflammasome priming in intravascular monocytes were associated with IL-1β production within the occluded middle cerebral artery within 4.5 hours of stroke onset. IL-1β release coincided with increased neutrophil-attracting chemokines (C-X-C motif chemokine ligand 1 [CXCL1], IL-8). Locally activated neutrophils formed neutrophil extracellular traps (NETs) within the ischemic vasculature, a hallmark of thromboinflammation. Postmortem analyses revealed NET deposition within ischemic brain parenchyma. INTERPRETATION: These findings indicate increased IL-1β expression and enhanced NET formation within the cerebral circulation in stroke caused by large vessel occlusion, suggesting that these mechanisms might contribute to early stroke pathophysiology and represent potential targets for immunomodulatory strategies. ANN NEUROL 2026;100:824-840.
SN - 0364-5134
SN - 1531-8249
ER -