Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production.



Emsley, Hedley CA ORCID: 0000-0003-0129-4488, Smith, Craig J ORCID: 0000-0002-9078-9919, Gavin, Carole M, Georgiou, Rachel F ORCID: 0000-0002-0920-0602, Vail, Andy ORCID: 0000-0001-8274-2726, Barberan, Elisa M, Illingworth, Karen ORCID: 0000-0001-9456-2298, Scarth, Sylvia, Wickramasinghe, Vijitha, Hoadley, Margaret E
et al (show 3 more authors) (2007) Clinical outcome following acute ischaemic stroke relates to both activation and autoregulatory inhibition of cytokine production. BMC neurology, 7 (1). 5-.

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Abstract

<h4>Background</h4>As critical mediators of local and systemic inflammatory responses, cytokines are produced in the brain following ischaemic stroke. Some have been detected in the circulation of stroke patients, but their role and source is unclear. Focusing primarily on interleukin(IL)-1-related mechanisms, we serially measured plasma inflammatory markers, and the production of cytokines by whole blood, from 36 patients recruited within 12 h and followed up to 1 year after acute ischaemic stroke (AIS).<h4>Results</h4>Admission plasma IL-1 receptor antagonist (IL-1ra) concentration was elevated, relative to age-, sex-, and atherosclerosis-matched controls. IL-1beta, soluble IL-1 receptor type II, tumour necrosis factor (TNF)-alpha, TNF-RII, IL-10 and leptin concentrations did not significantly differ from controls, but peak soluble TNF receptor type I (sTNF-RI) in the first week correlated strongly with computed tomography infarct volume at 5-7 days, mRS and BI at 3 and 12 months. Neopterin was raised in patients at 5-7 d, relative to controls, and in subjects with significant atherosclerosis. Spontaneous IL-1beta, TNF-alpha and IL-6 gene and protein expression by blood cells was minimal, and induction of these cytokines by lipopolysaccharide (LPS) was significantly lower in patients than in controls during the first week. Minimum LPS-induced cytokine production correlated strongly with mRS and BI, and also with plasma cortisol.<h4>Conclusion</h4>Absence of spontaneous whole blood gene activation or cytokine production suggests that peripheral blood cells are not the source of cytokines measured in plasma after AIS. Increased plasma IL-1ra within 12 h of AIS onset, the relationship between sTNF-RI and stroke severity, and suppressed cytokine induction suggests early activation of endogenous immunosuppressive mechanisms after AIS.

Item Type: Article
Additional Information: Published: 28 February 2007. 12 pages (page numbers not for citation purposes).
Uncontrolled Keywords: Humans, Brain Ischemia, Inflammation, Cytokines, Homeostasis, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Stroke, Biomarkers, Outcome Assessment, Health Care
Subjects: ?? RC0321 ??
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 27 Jun 2008 13:32
Last Modified: 16 Mar 2024 13:08
DOI: 10.1186/1471-2377-7-5
Publisher's Statement : © 2007 Emsley et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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URI: https://livrepository.liverpool.ac.uk/id/eprint/722