Distinct cytokine responses in central and systemic compartments after subarachnoid haemorrhage
Distinct cytokine responses in central and systemic compartments after subarachnoid haemorrhage
Introduction: neuroinflammation may contribute to outcomes following subarachnoid haemorrhage (SAH). Human cerebrospinal fluid (CSF) cytokine data is limited and its relationship with systemic inflammation is unknown. This study compares the inflammatory responses in CSF and plasma compartments, and their associations with outcome.
Methods: ten cytokines were measured in CSF and plasma from 98 SAH patients and 18 control patients. Outcome was assessed with the modified Rankin scale (mRS) and Subarachnoid Haemorrhage Outcome Tool (SAHOT) at days 7, 28, 90 and 180. Regression analyses and principal component analysis (PCA) were performed.
Results: median levels of all CSF cytokines and plasma IL-6 were higher in SAH patients than controls (p < 0.001). Plasma IL-6 peaked earlier (3 days after SAH) than CSF cytokines (7–9 days after SAH). On day 7, CSF levels were greater than plasma levels for all cytokines (p < 0.001). There was no correlation between individual cytokines in the plasma and CSF. Only plasma IL-6 levels correlated with long-term outcome (mRS (p = 0.009) and SAHOT (p = 0.007) at day 180), accounting for WFNS and blood volume. Seven principal components of cytokines had an eigenvalue greater than 1. Only the first plasma principal component (dominated by IL-6, IL-8, IL-12, IL-13, and TNF-α) was associated with outcomes (p < 0.05). Mediation analysis suggested the effects of WFNS and blood volume on outcome were not mediated by IL-6 or this principal component.
Conclusion: SAH provokes an inflammatory response in CSF and plasma. The response pattern is different and distinct in each compartment. Each compartment’s relationship with outcomes differ, suggesting separate roles in SAH pathophysiology. Plasma IL-6 is independently associated with outcomes.
Blood Brain Interface, Cerebrospinal Fluid, Cytokines, Inflammation, Subarachnoid Haemorrhage, Vasospasm
Bandyopadhyay, Soham
be755ba2-c8f7-401c-af9e-16a77506fe4d
Gaastra, Ben
c7b7f371-706b-4d59-9150-94e8f254e205
Zolnourian, Ardalan
7cd6d7ef-7b29-4277-98c4-2cba161e1892
Garland, Patrick
1d24a0cc-81f2-4ef1-82bd-77d2510e59d6
Wu, Chieh-Hsi
ace630c6-2095-4ade-b657-241692f6b4d3
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Bulters, Diederik
d6f9644a-a32f-45d8-b5ed-be54486ec21d
25 March 2025
Bandyopadhyay, Soham
be755ba2-c8f7-401c-af9e-16a77506fe4d
Gaastra, Ben
c7b7f371-706b-4d59-9150-94e8f254e205
Zolnourian, Ardalan
7cd6d7ef-7b29-4277-98c4-2cba161e1892
Garland, Patrick
1d24a0cc-81f2-4ef1-82bd-77d2510e59d6
Wu, Chieh-Hsi
ace630c6-2095-4ade-b657-241692f6b4d3
Galea, Ian
66209a2f-f7e6-4d63-afe4-e9299f156f0b
Bulters, Diederik
d6f9644a-a32f-45d8-b5ed-be54486ec21d
Bandyopadhyay, Soham, Gaastra, Ben, Zolnourian, Ardalan, Garland, Patrick, Wu, Chieh-Hsi, Galea, Ian and Bulters, Diederik
(2025)
Distinct cytokine responses in central and systemic compartments after subarachnoid haemorrhage.
Translational Stroke Research, [106184].
(doi:10.1007/s12975-025-01348-y).
Abstract
Introduction: neuroinflammation may contribute to outcomes following subarachnoid haemorrhage (SAH). Human cerebrospinal fluid (CSF) cytokine data is limited and its relationship with systemic inflammation is unknown. This study compares the inflammatory responses in CSF and plasma compartments, and their associations with outcome.
Methods: ten cytokines were measured in CSF and plasma from 98 SAH patients and 18 control patients. Outcome was assessed with the modified Rankin scale (mRS) and Subarachnoid Haemorrhage Outcome Tool (SAHOT) at days 7, 28, 90 and 180. Regression analyses and principal component analysis (PCA) were performed.
Results: median levels of all CSF cytokines and plasma IL-6 were higher in SAH patients than controls (p < 0.001). Plasma IL-6 peaked earlier (3 days after SAH) than CSF cytokines (7–9 days after SAH). On day 7, CSF levels were greater than plasma levels for all cytokines (p < 0.001). There was no correlation between individual cytokines in the plasma and CSF. Only plasma IL-6 levels correlated with long-term outcome (mRS (p = 0.009) and SAHOT (p = 0.007) at day 180), accounting for WFNS and blood volume. Seven principal components of cytokines had an eigenvalue greater than 1. Only the first plasma principal component (dominated by IL-6, IL-8, IL-12, IL-13, and TNF-α) was associated with outcomes (p < 0.05). Mediation analysis suggested the effects of WFNS and blood volume on outcome were not mediated by IL-6 or this principal component.
Conclusion: SAH provokes an inflammatory response in CSF and plasma. The response pattern is different and distinct in each compartment. Each compartment’s relationship with outcomes differ, suggesting separate roles in SAH pathophysiology. Plasma IL-6 is independently associated with outcomes.
Text
s12975-025-01348-y
- Version of Record
More information
Accepted/In Press date: 19 March 2025
Published date: 25 March 2025
Keywords:
Blood Brain Interface, Cerebrospinal Fluid, Cytokines, Inflammation, Subarachnoid Haemorrhage, Vasospasm
Identifiers
Local EPrints ID: 500548
URI: http://eprints.soton.ac.uk/id/eprint/500548
ISSN: 1868-601X
PURE UUID: 10c64e4a-fb04-4f8b-8aa8-f02c649d0ae7
Catalogue record
Date deposited: 06 May 2025 16:34
Last modified: 22 Aug 2025 02:44
Export record
Altmetrics
Contributors
Author:
Soham Bandyopadhyay
Author:
Ardalan Zolnourian
Author:
Diederik Bulters
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics