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Cited by 2,252Vagus Nerve Stimulation ResearchStress Responses and CortisolCancer, Stress, Anesthesia, and Immune Response

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The Sympathetic Nerve—An Integrative Interface between Two Supersystems: The Brain and the Immune System

Elenkov, Ilia J., Wilder, Ronald L., Chrousos, George P., Vizi, E. Sylvester·2000·Pharmacological Reviews
DOI 10.1016/s0031-6997(24)01470-4
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Abstract

The brain and the immune system are the two major adaptive systems of the body. During an immune response the brain and the immune system "talk to each other" and this process is essential for maintaining homeostasis. Two major pathway systems are involved in this cross-talk: the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). This overview focuses on the role of SNS in neuroimmune interactions, an area that has received much less attention than the role of HPA axis. Evidence accumulated over the last 20 years suggests that norepinephrine (NE) fulfills the criteria for neurotransmitter/neuromodulator in lymphoid organs. Thus, primary and secondary lymphoid organs receive extensive sympathetic/noradrenergic innervation. Under stimulation, NE is released from the sympathetic nerve terminals in these organs, and the target immune cells express adrenoreceptors. Through stimulation of these receptors, locally released NE, or circulating catecholamines such as epinephrine, affect lymphocyte traffic, circulation, and proliferation, and modulate cytokine production and the functional activity of different lymphoid cells. Although there exists substantial sympathetic innervation in the bone marrow, and particularly in the thymus and mucosal tissues, our knowledge about the effect of the sympathetic neural input on hematopoiesis, thymocyte development, and mucosal immunity is extremely modest. In addition, recent evidence is discussed that NE and epi…

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  • The size and quality of the intestinal mucus layer is believed to be mediated by sympathetic innervation where mucosal immune system modulation and microbial composition and behavior alterations were seen.

    “The size and quality of the intestinal mucus layer is believed to be mediated by sympathetic innervation where mucosal immune system modulation (Elenkov et al., 2000) and microbial composition and behavior alterations (commensal and pathogenic) were seen (Macfarlane and Dillon, 2007;Rhee et al., 2009)”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Elenkov et al., 2000

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Metadata

Authors
Elenkov, I. J., Wilder, R. L., Chrousos, G. P., & Vizi, E. S.
Affiliations
  • National Institutes of Health (US)
  • Hungarian Academy of Sciences (HU)
ORCID
Vizi, E. Sylvester
Venue
Pharmacological Reviews
Publisher
Elsevier BV
Published
2000-12
Volume
52
Issue
4
Pages
595-638
ISSN
0031-6997 (ISSN-L)
DOI
10.1016/s0031-6997(24)01470-4
OpenAlex
W2135514207
Cited by
2,252
References
8
Citations by year
2026: 47 · 2025: 67 · 2024: 62 · 2023: 86 · 2022: 79 · 2021: 86 · 2020: 83 · 2019: 88 · 2018: 76 · 2017: 82 · 2016: 116 · 2015: 98 · 2014: 90 · 2013: 89 · 2012: 128
FWCI
30.23
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Pharmacological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Stress, Anesthesia, and Immune Response
Keywords
sympathetic nervous system, neuroimmune interactions, norepinephrine, catecholamines, adrenergic receptors, lymphoid organs, Th1/Th2 balance, cytokine production, antigen-presenting cells, mucosal immunity, thymus, bone marrow, hematopoiesis, hypothalamic-pituitary-adrenal axis
MeSH terms
Animals, Brain, Growth Substances, Hematopoiesis, Humans, Immune System, Immunity, Lymphocytes, Lymphoid Tissue, Neuropeptide Y, Norepinephrine, Receptors, Adrenergic, Sympathetic Nervous System, Signal Transduction, Cytokines

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