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

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“Inflammatory” Cytokines: Neuromodulators in Normal Brain?

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

DOI 10.1046/j.1471-4159.2000.740457.x

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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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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
DOI: 10.1046/j.1471-4159.2000.740457.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 693 d)
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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“Inflammatory” Cytokines: Neuromodulators in Normal Brain?

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