IL-33 modulates inflammatory brain injury but exacerbates systemic immunosuppression following ischemic strokeopen access
- Authors
- Zhang, S.R.[Zhang, S.R.]; Piepke, M.[Piepke, M.]; Chu, H.X.[Chu, H.X.]; Broughton, B.R.[Broughton, B.R.]; Shim, R.[Shim, R.]; Wong, C.H.[Wong, C.H.]; Lee, S.[Lee, S.]; Evans, M.A.[Evans, M.A.]; Vinh, A.[Vinh, A.]; Sakkal, S.[Sakkal, S.]; Arumugam, T.V.[Arumugam, T.V.]; Magnus, T.[Magnus, T.]; Huber, S.[Huber, S.]; Gelderblom, M.[Gelderblom, M.]; Drummond, G.R.[Drummond, G.R.]; Sobey, C.G.[Sobey, C.G.]; Kim, H.A.[Kim, H.A.]
- Issue Date
- 20-Sep-2018
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Keywords
- Cardiology; Immunotherapy; Inflammation; Mouse models; Stroke
- Citation
- JCI INSIGHT, v.3, no.18
- Indexed
- SCOPUS
- Journal Title
- JCI INSIGHT
- Volume
- 3
- Number
- 18
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/18517
- DOI
- 10.1172/jci.insight.121560
- ISSN
- 2379-3708
- 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 1L-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 1L-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 stroke, The data indicate that a Th2-promoting agent can provide neuroprotection without adverse systemic effects when given in combination with antibiotics.
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Collections - Pharmacy > Department of Pharmacy > 1. Journal Articles
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