Chronic Interleukin-1β Expression in Mouse Brain Leads to Leukocyte Infiltration and Neutrophil-Independent Blood–Brain Barrier Permeability without Overt Neurodegeneration
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The proinflammatory cytokine interleukin-1beta (IL-1beta) plays a significant role in leukocyte recruitment to the CNS. Although acute effects of IL-1beta signaling in the mouse brain have been well described, studies elucidating the downstream effects of sustained upregulation have been lacking. Using the recently described IL-1beta(XAT) transgenic mouse model, we triggered sustained unilateral hippocampal overexpression of IL-1beta. Transgene induction led to blood-brain barrier leakage, induction of MCP-1 (monocyte chemoattractant protein 1) (CCL2), ICAM-1 (intercellular adhesion molecule 1), and dramatic infiltration of CD45-positive leukocytes comprised of neutrophils, T-cells, macrophages, and dendritic cells. Despite prolonged cellular infiltration of the hippocampus, there was no evidence of neuronal degeneration. Surprisingly, neutrophils were observed in the hippocampal parenchyma as late as 1 year after transgene induction. Their presence was coincident with upregulation of the potent neutrophil chemotactic chemokines KC (keratinocyte-derived chemokine) (CXCL1) and MIP-2 (macrophage inflammatory protein 2) (CXCL2). Knock-out of their sole receptor CXCR2 abrogated neutrophil infiltration but failed to reduce leakage of the blood-brain barrier.
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IL-1β induces significant recruitment of neutrophils.
“Previous work from our lab has shown that IL-1β induces significant recruitment of neutrophils [30]”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [30]
IL-1β induces recruitment of CD4+ and CD8+ T cells.
“we have previously shown that IL-1β induces recruitment of CD4+ and CD8+ T cells [30].”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [30]
There was minimal recruitment of CD45hi peripheral immune cells (CD11b+ and CD11b−) in APP/PS1-Phe mice.
“In agreement with our previous observations [28, 30] there was minimal recruitment of CD45hi peripheral immune cells (CD11b+ and CD11b−) in APP/PS1-Phe mice”
From IL-1β-driven amyloid plaque clearance is associated with an expansion of transcriptionally reprogrammed microglia (2019) · cites this paper as [30]
The ‘Diverse leukocyte populations are recruited by IL-1β expression’ section reports a fivefold increase in CD45hi/CD11b+ cells in IL-1β XAT mice, not minimal recruitment in APP/PS1-Phe mice. Our copy does not address APP/PS1-Phe mice or the claimed CD11b+ and CD11b− recruitment pattern; the finding in a different mouse model does not establish a contradiction. (LLM, conf=0.76)
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- Authors
- Shaftel, S. S., Carlson, T. J., Olschowka, J. A., Kyrkanides, S., Matousek, S. B., & O'Banion, M. K.
- Affiliations
- University of Rochester Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2007-08-29
- Volume
- 27
- Issue
- 35
- Pages
- 9301-9309
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6673122
- OpenAlex
- W2094676206
- Cited by
- 243
- References
- 55
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 14 · 2021: 13 · 2020: 10 · 2019: 18 · 2018: 22 · 2017: 9 · 2016: 15 · 2015: 13 · 2014: 19 · 2013: 19 · 2012: 10
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Rochester
- National Institutes of Health
- National Institute of General Medical Sciences (GM 07356, T32GM007356)
- National Institute of Neurological Disorders and Stroke (NS048522, R29NS033553, NS 33553, R21NS048522, R01NS033553)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- IL-1β, chronic neuroinflammation, blood-brain barrier permeability, leukocyte infiltration, neutrophils, CXCR2, CXCL1, CXCL2, MCP-1, ICAM-1, hippocampus, transgenic mouse model, neurodegeneration, chemokines
- MeSH terms
- Animals, Blood-Brain Barrier, Hippocampus, Leukocytes, Mice, Inbred C57BL, Mice, Transgenic, Neutrophils, Monokines, Up-Regulation, Leukocyte Common Antigens, Intercellular Adhesion Molecule-1, Chemokine CCL2, Mice, Interleukin-1beta, Chemokine CXCL2
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