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Reflex control of immunity
Open accessAbstract
Inflammation can cause damage and even death. What controls this primitive and potentially lethal innate immune response to injury and infection? Molecular and neurophysiological studies during the past decade have revealed a pivotal answer: immunity is coordinated by neural circuits that operate reflexively. The afferent arc of the reflex consists of nerves that sense injury and infection. This activates efferent neural circuits, including the cholinergic anti-inflammatory pathway, that modulate immune responses and the progression of inflammatory diseases. It might be possible to develop therapeutics that target neural networks for the treatment of inflammatory disorders.
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“Interestingly, evidence suggests that activation of the parasympathetic nervous system also can modulate the activity of the immune system via alterations in vagal release of acetylcholine from T cells (Tracey, 2009).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Tracey, 2009
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“Additional evidence suggests that the parasympathetic nervous system modulates immune responses at a regional level through both the efferent and afferent fibers of the vagus nerve, enabling it to prevent excessive inflammation”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Tracey, 2009
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“For example, motor vagus nerve stimulation attenuates the activation of NFκB following an immune challenge (Tracey, 2009).”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Tracey, 2009
In the citing paper
“ACh binds to α-7-nicotinic ACh receptors of those macrophages to inhibit the TNF-α (69).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [69]
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“with evidence that vagal activity can modulate immune responses at a regional level through both the efferent and afferent fibers of the vagus nerve, to prevent excessive inflammation”
From Sleep health: Reciprocal regulation of sleep and innate immunity (2017) · cites this paper as Tracey, 2009
In the citing paper
“Multiple non-exclusive pathways participate in the activation of the HPA axis upon cerebral or peripheral immune challenges. When an immunogenic insult takes place in the brain, various inflammatory mediators produced locally may trigger the HPA axis.”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [21]
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Citations
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Into the Future: Autonomic Neuropathy, MicroRNAs, and Gene Therapy
Alevizos, I., Chiorini, J. A., & Nikolov, N. P. (2011) · Springer eBooks · doi:10.1007/978-1-60327-957-4_34
“ergic anti-inflammatory pathway” [5] indicates”
Cholinergic nervous system as therapeutic approach for the treatment of arthritis
van Maanen, M. A. (2009) · Data Archiving and Networked Services (DANS)
Regenerating the brain: Stem cell differentiation and cholinergic dysfunction in Alzheimer disease
Malmsten, L. (2014) · Figshare
Putting Out Fat's Fire with the Cholinergic Antiinflammatory Pathway
Swarbrick, M. M. (2011) · Endocrinology · doi:10.1210/en.2011-0041
Sistema nervioso central y regulación de la respuesta inmune
Vergara, C. (2011) · Avances en Ciencias Veterinarias · doi:10.5354/acv.v26i1-2.17531
“En los últimos años se ha hecho evidente que el sistema inmune no es un sistema completamente autónomo, puesto que los órganos linfoides están inervados por neuronas colinérgicas, catecolaminérgicas, peptidérgicas y otras neuronas (Tracey, 2009).”
BackgroundPlacebo: no longer a phantom response
Pasternak, C. A. (2011) · Interdisciplinary Science Reviews · doi:10.1179/030801811x12941390545762
“Recently, it was discovered that acetyl choline released by the vagus nerve, that is situated in the brain stem, regulates the activity not just of heart, intestine and other organs through afferent and efferent parasympathetic pathways, but also the immune system (Tracey 2002; 2009).”
BackgroundReceptor strategy for brain ischemia
Osherovich, L. Z. (2011) · Science-Business eXchange · doi:10.1038/scibx.2011.329
Colombo, J., Arora, R. R., DePace, N. L., & Vinik, A. I. (2014) · Springer eBooks · doi:10.1007/978-3-319-07371-2_14
Correia, N. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/enhk-4170
Rocha, J. A. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2013.tde-22012014-122449
Impact of genetic variability on early immune reactions following nerve injury
Lindblom, R. P. F. (2013) · Figshare
Space Travel: An Integrative View from the Scientists of the Topical Team “Stress and Immunity”
Baatout, S., Choukèr, A., Kaufmann, I., Montano, N., Praun, S., de Quervain, D. J. ‐., Roozendaal, B., Schelling, G., & Thiel, M. (2011) · Springer eBooks · doi:10.1007/978-3-642-22272-6_2
“Moreover, in the case of the immune system for example, changes can infl uence other physiological systems, and even feedback with neural pathways in a bidirectional manner (Tracey 2009 ) .”
BackgroundPerspective and Direction for Future Research
Farooqui, A. A. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7318-3_10
dos Santos, F. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.5.2016.tde-02052016-084732
Metadata
- Authors
- Tracey, K. J.
- Affiliations
- Feinstein Institute for Medical Research (US)
- Corresponding author
- Tracey, Kevin J.
- ORCID
- Tracey, Kevin J.
- Venue
- Nature Reviews Immunology
- Published
- 2009-06
- Volume
- 9
- Issue
- 6
- Pages
- 418-428
- ISSN
- 1474-1733 (ISSN-L)
- 1474-1741
- PMC
- PMC4535331
- OpenAlex
- W2029051866
- Cited by
- 1,154
- References
- 102
- Citations by year
- 2026: 55 · 2025: 61 · 2024: 49 · 2023: 66 · 2022: 71 · 2021: 77 · 2020: 73 · 2019: 71 · 2018: 66 · 2017: 71 · 2016: 80 · 2015: 75 · 2014: 70 · 2013: 81 · 2012: 68
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature reviews. Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Feinstein Institutes for Medical Research
- National Institute of General Medical Sciences (R01GM057226)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Keywords
- cholinergic anti-inflammatory pathway, acetylcholine, inflammatory cytokines, neural circuits, innate immunity, neuroimmune regulation, inflammatory diseases
- MeSH terms
- Animals, Cardiovascular Physiological Phenomena, Catecholamines, Efferent Pathways, Homeostasis, Humans, Hypertension, Immunity, Innate, Inflammation, Receptors, Cholinergic, Reflex, Neuroimmunomodulation
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