In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis
Open accessAbstract
Interleukin-1 (IL-1), an inflammatory cytokine overexpressed in the neuritic plaques of Alzheimer's disease, activates astrocytes and enhances production and processing of beta-amyloid precursor protein (beta-APP). Activated astrocytes, overexpressing S100 beta, are a prominent feature of these neuritic plaques, and the neurite growth-promoting properties of S100 beta have been implicated in the formation of dystrophic neurites overexpressing beta-APP in neuritic plaques. These facts collectively suggest that elevated levels of the inflammatory cytokine IL-1 drive S100 beta and beta-APP overexpression and dystrophic neurite formation in Alzheimer's disease. To more directly assess this driver potential for IL-1, we analyzed IL-1 induction of S100 beta expression in vivo and in vitro, and of beta-APP expression in vivo. Synthetic IL-1 beta was injected into the right cerebral hemispheres of 13 rats. Nine additional rats were injected with phosphate-buffered saline, and seven rats served as uninjected controls. The number of astrocytes expressing detectable levels of S100 beta in tissue sections from IL-1-injected brains was 1.5 fold that of either control group (p < 0.01), while tissue S100 beta levels were approximately threefold that of controls (p < 0.05). The tissue levels of two beta-APP isoforms (approximately 130 and 135 kDa) were also significantly elevated in IL-1-injected brains (p < 0.05). C6 glioma cells, treated in vitro for 24 h with either IL-1 beta or IL-1 alpha, showed significant increases in both S100 beta and S100 beta mRNA levels. These results provide evidence that IL-1 upregulates both S100 beta and beta-APP expression, in vivo and vitro, and support the idea that overexpression of IL-1 in Alzheimer's disease drives astrocytic overexpression of S100 beta, favoring the growth of dystrophic neurites necessary for evolution of diffuse amyloid deposits into neuritic beta-amyloid plaques.
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IL-1β injection into the cerebral hemisphere increases Aβ-APP proteins in wild-type rats.
“IL-1β injection into the cerebral hemisphere increases Aβ-APP proteins in wild-type rats (234).”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [234]
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- Authors
- Sheng, J. G., Ito, K., Skinner, R. D., Mrak, R. E., Rovnaghi, C. R., van Eldik, L. J., & Griffin, W. S. T.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Griffin, W.Sue T.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 1996-09
- Volume
- 17
- Issue
- 5
- Pages
- 761-766
- ISSN
- 0197-4580 (ISSN-L)
- PMC
- PMC3886636
- OpenAlex
- W1994394172
- Cited by
- 269
- References
- 32
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 11 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 7 · 2013: 11 · 2012: 10
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r01ns027414-01a1, 5p01ag010208-05)
- National Institute on Aging (AG 10208, AG 12411, P01AG012411)
- National Institute of Neurological Disorders and Stroke (NS27414)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- interleukin-1, Alzheimer's disease, S100β, amyloid precursor protein, astrocytes, neuritic plaques, dystrophic neurites, neuroinflammation, IL-1β, IL-1α, C6 glioma cells, amyloid plaques
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Brain Chemistry, Brain Neoplasms, Glioma, Humans, Immunohistochemistry, Interleukin-1, S100 Proteins, Tumor Cells, Cultured, Blotting, Northern, Blotting, Western, Up-Regulation, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, In Situ Hybridization, Rats
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