Cited by 400Vagus Nerve Stimulation ResearchTryptophan and brain disordersNeuroinflammation and Neurodegeneration Mechanisms

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Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?

Dantzer, Robert, Konsman, Jan-Pieter, Bluthé, Rose-Marie, Kelley, Keith W·2000·Autonomic Neuroscience

DOI 10.1016/s1566-0702(00)00220-4

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Abstract

The first studies carried out on the mechanisms by which peripheral immune stimuli signal the brain to induce fever, activation of the hypothalamic-pituitary-adrenal axis and sickness behavior emphasized the importance of fenestrated parts of the blood-brain barrier known as circumventricular organs for allowing blood-borne proinflammatory cytokines to act on brain functions. The discovery in the mid-1990s that subdiaphragmatic section of the vagus nerves attenuates the brain effects of systemic cytokines, together with the demonstration of an inducible brain cytokine compartment shifted the attention from circumventricular organs to neural pathways in the transmission of the immune message to the brain. Since then, neuroanatomical studies have confirmed the existence of a fast route of communication from the immune system to the brain via the vagus nerves. This neural pathway is complemented by a humoral pathway that involves cytokines produced at the level of the circumventricular organs and the choroid plexus and at the origin of a second wave of cytokines produced in the brain parenchyma. Depending on their source, these locally produced cytokines can either activate neurons that project to specific brain areas or diffuse by volume transmission into the brain parenchyma to reach their targets. Activation of neurons by cytokines can be direct or indirect, via prostaglandins. The way the neural pathway of transmission interacts with the humoral pathway remains to be elucidated.

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Authors: Dantzer, R., Konsman, J.-P., Bluthé, R.-M., & Kelley, K. W.
Affiliations: Inserm (FR)
University of Illinois Urbana-Champaign (US)
Corresponding author: Dantzer, Robert
ORCID: Dantzer, Robert
Konsman, Jan-Pieter
Kelley, Keith W
Venue: Autonomic Neuroscience
Publisher: Elsevier BV
Published: 2000-12
Volume: 85
Issue: 1-3
Pages: 60-65
ISSN: 1566-0702 (ISSN-L)
DOI: 10.1016/s1566-0702(00)00220-4
OpenAlex: W2011871032
Cited by: 400
References: 65
Citations by year: 2026: 16 · 2025: 21 · 2024: 18 · 2023: 20 · 2022: 18 · 2021: 19 · 2020: 19 · 2019: 19 · 2018: 14 · 2017: 16 · 2016: 14 · 2015: 18 · 2014: 17 · 2013: 17 · 2012: 17
FWCI: 1.25
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Autonomic Neuroscience (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: National Institutes of Health (5k08mh001258-05)
National Institute of Mental Health (R01MH051569, MH-1258, MH51569)
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: neuroimmune interactions, vagus nerve, cytokine signaling, circumventricular organs, choroid plexus, fever, sickness behavior, hypothalamic-pituitary-adrenal axis, inflammatory cytokines, volume transmission, prostaglandins, brain cytokines
MeSH terms: Animals, Antibody Formation, Brain, Neural Pathways, Vagus Nerve, Neuroimmunomodulation

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Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?

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