Cited by 506Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersCytokine Signaling Pathways and Interactions

“Inflammatory” Cytokines: Neuromodulators in Normal Brain?

Vitkovic, Ljubisa, Bockaert, Joël, Jacque, Claude·2000·Journal of Neurochemistry

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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Registry

Crossref · 10.1046/j.1471-4159.2000.740457.x

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149 of 149 references verified0 citation errors · 0 not checkable

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  • When PAMPS activate TLRs in the circumventricular organs or choroid plexus, macrophage-like cells produce proinflammatory cytokines that can enter the brain by volume diffusion.

    “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

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Authors
Vitkovic, L., Bockaert, J., & Jacque, C.
Affiliations
Centre National de la Recherche Scientifique (FR)
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
  • Health Sciences › Medicine › Oncology › 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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