Central Nervous System-Initiated Inflammation and Neurotrophism in Trauma: IL-1β Is Required for the Production of Ciliary Neurotrophic Factor
Open accessAbstract
Injury to the CNS results in the production and accumulation of inflammatory cytokines within this tissue. The origin and role of inflammation within the CNS remains controversial. In this paper we demonstrate that an acute trauma to the mouse brain results in the rapid elevation of IL-1beta. This increase is detectable by 15 min after injury and significantly precedes the influx of leukocytes that occurs hours after. To confirm that IL-1beta up-regulation is initiated by cells within the CNS, in situ hybridization for cytokine transcript was combined with cell type immunohistochemistry. The results reveal parenchymal microglia to be the sole source of IL-1beta at 3 h postinjury. A role for CNS-initiated inflammation was addressed by examining the expression of the neurotrophic factor, ciliary neurotrophic factor (CNTF). Analysis of their temporal relationship suggests the up-regulation of CNTF by IL-1beta, which was confirmed through three lines of evidence. First, the application of IL-1 receptor antagonist into the lesion site attenuated the up-regulation of CNTF. Second, the examination of corticectomized animals genetically deficient for IL-1beta found no CNTF up-regulation. Third, the lack of CNTF elevation in IL-1beta null mice was rescued through exogenous application of IL-1beta into the lesion site. These findings provide the first evidence of the requirement for IL-1beta in the production of CNTF following CNS trauma, and suggest that inflammation can have a beneficial impact on the regenerative capacity of the CNS.
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IL-1beta and TNF-alpha can be harmful for cerebral elements but also play beneficial roles in the inflammatory response.
“Such cytokines can thus be harmful for the cerebral elements (138) but they also play beneficial roles in the inflammatory response (161–163).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [162]
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- Authors
- Herx, L. M., Rivest, S., & Yong, V. W.
- Affiliations
- University of Calgary (CA)
- Université Laval (CA)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-08
- Volume
- 165
- Issue
- 4
- Pages
- 2232-2239
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2156066294
- Cited by
- 190
- References
- 54
- Citations by year
- 2023: 2 · 2022: 4 · 2021: 1 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 4 · 2013: 9 · 2012: 10
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- central nervous system injury, traumatic brain injury, IL-1β, ciliary neurotrophic factor, microglia, neuroinflammation, neurotrophic factors, interleukin-1 receptor antagonist, corticectomy, central nervous system regeneration, inflammatory cytokines
- MeSH terms
- Animals, Brain, Brain Injuries, Female, Frontal Lobe, Interleukin-1, Mice, Inbred C57BL, RNA, Messenger, Sialoglycoproteins, Injections, Intralesional, Up-Regulation, Cytokines, Receptors, Interleukin-1, Mice, Knockout, Ciliary Neurotrophic Factor, Mice, Interleukin 1 Receptor Antagonist Protein
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