IL-33 modulates inflammatory brain injury but exacerbates systemic immunosuppression following ischemic stroke

JCI Insight
Shenpeng R ZhangHyun Ah Kim

Abstract

Stroke triggers a complex inflammatory process in which the balance between pro- and antiinflammatory mediators is critical for the development of the brain infarct. However, systemic changes may also occur in parallel with brain inflammation. Here we demonstrate that administration of recombinant IL-33, a recently described member of the IL-1 superfamily of cytokines, promotes Th2-type effects following focal ischemic stroke, resulting in increased plasma levels of Th2-type cytokines and fewer proinflammatory (3-nitrotyrosine+F4/80+) microglia/macrophages in the brain. These effects of IL-33 were associated with reduced infarct size, fewer activated microglia and infiltrating cytotoxic (natural killer-like) T cells, and more IL-10-expressing regulatory T cells. Despite these neuroprotective effects, mice treated with IL-33 displayed exacerbated post-stroke lung bacterial infection in association with greater functional deficits and mortality at 24 hours. Supplementary antibiotics (gentamicin and ampicillin) mitigated these systemic effects of IL-33 after stroke. Our findings highlight the complex nature of the inflammatory mechanisms differentially activated in the brain and periphery during the acute phase after ischemic stro...Continue Reading

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Citations

Mar 6, 2019·Acta neurologica Belgica·Kun FuYunan Bai
May 28, 2019·Clinical and Experimental Immunology·F C Bennett, A V Molofsky
Nov 12, 2019·Translational Stroke Research·Raymond ShimConnie H Y Wong
Aug 3, 2019·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Natalia KolosowskaHiramani Dhungana
Dec 19, 2019·Frontiers in Immunology·Yijie WangAnwen Shao
May 21, 2019·Free Radical Research·Pietro ScicchitanoMarco Matteo Ciccone
Dec 21, 2020·Trends in Pharmacological Sciences·Shenpeng R ZhangChristopher G Sobey
Jan 21, 2021·CNS Neuroscience & Therapeutics·Huan WangXiangjian Zhang
May 11, 2021·Journal of Molecular Neuroscience : MN·Yi-Sha GuoXia Bi
Jun 4, 2021·Frontiers in Immunology·Yun SunXiaofeng Yang
Aug 7, 2021·Journal of Multidisciplinary Healthcare·Meirong Xu, Ganlin Wu
Sep 21, 2021·Biochemical Pharmacology·Drishti P GhelaniT Michael De Silva
Oct 9, 2021·Stroke; a Journal of Cerebral Circulation·Shenpeng R ZhangThanh G Phan

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Methods Mentioned

BETA
flow cytometry
PCR
blood collection

Software Mentioned

FACSDiva
GraphPad
GraphPad Prism
NIH ImageJ
FlowJo

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