An Age-Related Decline in Interleukin-10 May Contribute to the Increased Expression of Interleukin-6 in Brain of Aged Mice
Abstract
OBJECTIVES: The DNA-binding activity of nuclear factor kappaB (NFkappaB) is elevated in brain of aged mice, resulting in elevated levels of the inflammatory cytokine interleukin (IL)-6. The purpose of this study was to determine if in the brain of aged mice a decrease in the anti-inflammatory cytokine IL-10 contributes to the increase in IL-6. METHODS: In initial studies coronal brain sections and glial cells from adult (6-months-old) and aged (24-months-old) mice were incubated in the presence or absence of lipopolysaccharide (LPS) and the concentrations of IL-6 and IL-10 in supernatants were determined. In subsequent studies, the effect of recombinant murine IL-10 on constitutive and inducible NFkappaB activity, IL-6 mRNA expression and IL-6 protein secretion by glia cultured from brains of adult and aged mice was determined. RESULTS: Coronal brain sections and glia from aged mice secreted more IL-6 and less IL-10 than brain sections and glia from adults. This effect of age was evident in the absence and presence of LPS and suggested that a decrease in IL-10 production permitted increased IL-6 production. Consistent with this idea, treatment of glia from aged mice with recombinant IL-10 decreased both constitutive and inducible binding of NFkappaB to the IL-6 gene promoter. The decrease in NFkappaB activity was associated with a reduction of IL-6 mRNA and protein. Exogenous IL-10, however, had no effect on NFkappaB activity, which was undetectable in unstimulated glia from adult mice, and did not decrease steady-state levels of IL-6 mRNA or IL-6 protein secretion. CONCLUSIONS: Collectively, these studies suggest that IL-10 constrained IL-6 gene expression in the adult brain, but in the aged brain it decreased and thus enabled a cascade of intracellular events that increased expression of the IL-6 gene.
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In aged mice, increased production of IL-1β is associated with decreased production of the anti-inflammatory cytokine IL-10.
“For example, increased production of interleukin (IL)-1β in aged mice is associated with decreased production of the anti-inflammatory cytokine IL-10 (REF. 37).”
From From inflammation to sickness and depression: when the immune system subjugates the brain (2008) · cites this paper as [37]
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- Authors
- Ye, S.-M., & Johnson, R. W.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- ORCID
- Johnson, Rodney W.
- Venue
- Neuroimmunomodulation
- Publisher
- S. Karger AG
- Published
- 2001
- Volume
- 9
- Issue
- 4
- Pages
- 183-192
- ISSN
- 1021-7401 (ISSN-L)
- 1423-0216
- OpenAlex
- W2027041567
- Cited by
- 203
- References
- 1
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 9 · 2021: 17 · 2020: 6 · 2019: 6 · 2018: 5 · 2017: 12 · 2016: 7 · 2015: 16 · 2014: 5 · 2013: 15 · 2012: 9
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImmunoModulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r29dk051576-05)
- National Institute on Aging (AG 16710, R01AG016710)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-51576)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- IL-10, interleukin-6, brain aging, NF-κB, glial cells, neuroinflammation, anti-inflammatory cytokines, lipopolysaccharide, IL-6 expression, aged mice
- MeSH terms
- Aging, Animals, Brain, Brain Chemistry, Lipopolysaccharides, Mice, Inbred BALB C, Nerve Tissue Proteins, Neuroglia, Promoter Regions, Genetic, Recombinant Proteins, RNA, Messenger, Transcription, Genetic, Oligonucleotide Probes, Interleukin-6, NF-kappa B, Interleukin-10, Gene Expression Regulation, Developmental, Mice
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