The inflammatory reflex
Abstract
Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible 'hard-wired' neural systems.
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Early life stressful experiences might reduce inhibitory cholinergic neurotransmission, favoring inflammation persistence.
“Similarly, early life stressful experiences might reduce inhibitory cholinergic neurotransmission (25), favoring inflammation persistence (26).”
From Childhood maltreatment predicts adult inflammation in a life-course study (2007) · cites this paper as [26]
In response to pathogens and other injurious stimuli, TNF-α is produced by activated macrophages, dendritic cells, and other cells in the mucosa.
“For example, in response to pathogens and other injurious stimuli, tumor-necrosis factor-alpha (TNF-α), a cytokine, is produced by activated macrophages, dendritic cells, and other cells in the mucosa (3, 65).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [65]
The autonomic nervous system regulates peripheral cytokine production; parasympathetic nerves directly affect the immune system, sympathetic nerves affect it through noradrenaline secretion, and the vagus nucleus inhibits immune functions and cytokine production through acetylcholine.
“In addition, the autonomic nervous system regulates peripheral cytokine production. Parasympathetic nerves directly affect the immune system, while sympathetic nerves affect the immune system through NA secretion from the peripheral sympathetic ganglia. The vagus nucleus, which is located in the pons, inhibits immune functions and cytokine production through the secretion of Ach from the vagus ner”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [8]
The efferent arm of the inflammatory reflex, the cholinergic antiinflammatory pathway, is a highly robust mechanism for cytokine control.
“The efferent arm of the inflammatory reflex, now termed the cholinergic antiinflammatory pathway (14), is a highly robust mechanism for cytokine control.”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [14]
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- Authors
- Tracey, K. J.
- Affiliations
- Northwell Health (US)
- Corresponding author
- Tracey, Kevin J.
- ORCID
- Tracey, Kevin J.
- Venue
- Nature
- Published
- 2002-12
- Volume
- 420
- Issue
- 6917
- Pages
- 853-859
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1995525413
- Cited by
- 3,728
- References
- 79
- Citations by year
- 2026: 264 · 2025: 197 · 2024: 177 · 2023: 172 · 2022: 208 · 2021: 204 · 2020: 179 · 2019: 180 · 2018: 160 · 2017: 150 · 2016: 161 · 2015: 150 · 2014: 162 · 2013: 171 · 2012: 157
- FWCI
- 6.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- cholinergic anti-inflammatory pathway, cholinergic neurons, neuroimmune regulation, acute inflammation, inflammation treatment
- MeSH terms
- Animals, Antibodies, Monoclonal, Humans, Inflammation, Nervous System Physiological Phenomena, Reflex, Tumor Necrosis Factor-alpha, Vagus Nerve
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