The DOI matches its Crossref record; 149 of the 151 references it cites were found in a registry or an index.
“Inflammatory” Cytokines: Neuromodulators in Normal Brain?
Abstract
Abstract: If cytokines are constitutively expressed by and act on neurons in normal adult brain, then we may have to modify our current view that they are predominantly inflammatory mediators. We critically reviewed the literature to determine whether we could find experimental basis for such a modification. We focused on two “proinflammatory” cytokines, interleukin (IL)‐1 and tumor necrosis factor‐α (TNFα) because they have been most thoroughly investigated in shaping our current thinking. Evidence, although equivocal, indicates that the genes coding for these cytokines and their accessory proteins are expressed by neurons, in addition to glial cells, in normal brain. Their expression is region‐ and cell type‐specific. Furthermore, bioactive cytokines have been extracted from various regions of normal brain. The cytokines’ receptors selectively are present on all neural cell types, rendering them responsive to cytokine signaling. Blocking their action modifies multiple neural “house‐keeping” functions. For example, blocking IL‐1 or TNFα by several independent means alters regulation of sleep. This indicates that these cytokines likely modulate in the brain behavior of a normal organism. In addition, these cytokines are likely involved in synaptic plasticity, neural transmission, and Ca 2+ signaling. Thus, the evidence strongly suggests that these cytokines perform neural functions in normal brain. We therefore propose that they should be thought of as neuromodulators in addition to inflammatory mediators.
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“When PAMPS activate TLRs in the circumventricular organs or the choroid plexus, these macrophage-like cells produce proinflammatory cytokines, which can enter the brain by volume diffusion (Vitkovic et al, 2000).”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Vitkovic et al, 2000
Citations
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Metadata
- Authors
- Vitkovic, L., Bockaert, J., & Jacque, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Bockaert, Joël
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2000-02
- Volume
- 74
- Issue
- 2
- Pages
- 457-471
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2043217368
- Cited by
- 506
- References
- 151
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 6 · 2023: 11 · 2022: 7 · 2021: 11 · 2020: 11 · 2019: 17 · 2018: 13 · 2017: 14 · 2016: 19 · 2015: 18 · 2014: 25 · 2013: 18 · 2012: 29
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- cytokines, interleukin-1, TNF-α, neurons, neuroinflammation, cytokine receptors, sleep regulation, synaptic plasticity, calcium signaling, neuromodulation, normal brain function, glial cells
- MeSH terms
- Animals, Brain, Humans, Neurons, Reference Values, Cytokines, Neurotransmitter Agents, Inflammation Mediators
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