Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens

Sternberg, Esther M.

doi:10.1038/nri1810

Cited by 1,064Vagus Nerve Stimulation ResearchStress Responses and CortisolCancer, Stress, Anesthesia, and Immune Response

Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens

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Sternberg, Esther M.·2006·Nature Reviews Immunology

DOI 10.1038/nri1810PMC PMC1783839

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Abstract

The central nervous system (CNS) regulates innate immune responses through hormonal and neuronal routes. The neuroendocrine stress response and the sympathetic and parasympathetic nervous systems generally inhibit innate immune responses at systemic and regional levels, whereas the peripheral nervous system tends to amplify local innate immune responses. These systems work together to first activate and amplify local inflammatory responses that contain or eliminate invading pathogens, and subsequently to terminate inflammation and restore host homeostasis. Here, I review these regulatory mechanisms and discuss the evidence indicating that the CNS can be considered as integral to acute-phase inflammatory responses to pathogens as the innate immune system.

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The brain plays a critical role in appraising stressors and in modulating immune system reactivity to physical and social threat.
“the brain plays a critical role in appraising stressors, as well as in modulating immune system reactivity to physical and social threat”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Sternberg, 2006
The Abstract says the CNS regulates innate immune responses and describes physical and psychological stimuli activating a brain-mediated stress response that regulates immunity. It does not describe the brain appraising stressors or specifically address immune reactivity to social threat. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Although these regions do not directly regulate inflammatory activity, they have anatomical connections to lower level brain regions, including the hypothalamus and brainstem autonomic control nuclei, which influence systemic inflammation by modulating the activity of the HPA axis and SNS.
“Although these regions do not directly regulate inflammatory activity, they have anatomical connections to lower level brain regions, including the hypothalamus and brainstem autonomic control nuclei, which influence systemic inflammation by modulating the activity of the HPA axis and SNS”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Sternberg, 2006
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The parasympathetic nervous system modulates immune responses at a regional level through efferent and afferent fibers of the vagus nerve, enabling it to prevent excessive inflammation.
“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 Sternberg, 2006
Glucocorticoids regulate monocyte behavior through modulation of multiple signaling pathways.
“Glucocorticoids regulate monocyte behavior through modulation of multiple signaling pathways (22), so a thorough evaluation of the resistance hypothesis requires a model system that fully captures these dynamics in vivo.”
From A Functional Genomic Fingerprint of Chronic Stress in Humans: Blunted Glucocorticoid and Increased NF-κB Signaling (2008) · cites this paper as [22]
Vagal activity can modulate immune responses regionally through efferent and afferent fibers to prevent excessive inflammation.
“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 Sternberg, 2006

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Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
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“On the one hand, brain functioning regulates secretion of glucocorticoid hormones, and glucocorticoids can inhibit inflammation processes.(8) On the other hand, inflammation reduces glucocorticoid signaling, and reduced glucocorticoid signaling may lead to abnormal brain functioning.”
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Authors: Sternberg, E. M.
Affiliations: National Institutes of Health (US)
Corresponding author: Sternberg, Esther M.
Venue: Nature Reviews Immunology
Publisher: Springer Science and Business Media LLC
Published: 2006-04
Volume: 6
Issue: 4
Pages: 318-328
ISSN: 1474-1733 (ISSN-L)
1474-1741
DOI: 10.1038/nri1810
PMC: PMC1783839
OpenAlex: W2067949717
Cited by: 1,064
References: 145
Citations by year: 2026: 31 · 2025: 40 · 2024: 46 · 2023: 24 · 2022: 50 · 2021: 72 · 2020: 53 · 2019: 58 · 2018: 62 · 2017: 63 · 2016: 66 · 2015: 46 · 2014: 51 · 2013: 64 · 2012: 74
FWCI: 5.18
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)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (Z01MH002585)
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Psychiatry and Mental health › Cancer, Stress, Anesthesia, and Immune Response
Keywords: central nervous system, neuroimmune interactions, neuroendocrine stress response, sympathetic nervous system, parasympathetic nervous system, peripheral nervous system, pro-inflammatory response, inflammation resolution, host homeostasis, pathogen defense, toxic shock syndrome
MeSH terms: Animals, Central Nervous System, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Immunity, Innate, Models, Biological, Nervous System, Neuropeptides, Pituitary-Adrenal System, Peripheral Nervous System, Models, Immunological

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Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens

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