The neuroimmune basis of fatigue
Open accessAbstract
The exact nature and pathophysiology of fatigue remain largely elusive despite its high prevalence in physically ill patients. Studies on the relationship between the immune system and the central nervous system provide a new perspective on the mechanisms of fatigue. Inflammatory mediators that are released by activated innate immune cells at the periphery and in the central nervous system alter the metabolism and activity of neurotransmitters, generate neurotoxic compounds, decrease neurotrophic factors, and profoundly disturb the neuronal environment. The resulting alterations in fronto-striatal networks together with the activation of insula by inflammatory interoceptive stimuli underlie the many dimensions of fatigue including reduced incentive motivation, decreased behavioral flexibility, uncertainty about usefulness of actions, and awareness of fatigue.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inflammatory processes, including chronic peripheral inflammatory processes, can cause reduced synthesis of dopamine, serotonin and noradrenaline in brainstem neurons through biochemical cascades.
“This can be caused by inflammatory processes—not only of intra-cerebral origin, but also due to chronic peripheral inflammatory processes which, through well understood biochemical cascades, lead to reduced synthesis of dopamine, serotonin and noradrenaline in brainstem neurons (Dantzer et al., 2014).”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Dantzer et al., 2014
The “Neural basis of inflammation-induced fatigue” section (page not supplied) describes pathways by which peripheral inflammation affects brain neurotransmission, including reduced availability of dopamine and norepinephrine precursors and impaired serotonin transmission. It does not establish reduced synthesis of all three neurotransmitters in brainstem neurons, and it explicitly says that most neurotransmitter studies used acute inflammation, so their findings cannot be generalized to chronic inflammation. (LLM, conf=0.90)
Experimental — accuracy not yet measuredOne possible cause of fatigue is an impairment of monoaminergic brainstem projections with reduced availability of dopamine, serotonin and noradrenaline at their (sub)cortical target sites.
“There is now considerable evidence that one possible cause of fatigue is an impairment of these monoaminergic brainstem projections with reduced availability of dopamine, serotonin and noradrenaline at their (sub)cortical target sites (for review, see Dantzer et al., 2014).”
From Allostatic Self-efficacy: A Metacognitive Theory of Dyshomeostasis-Induced Fatigue and Depression (2016) · cites this paper as Dantzer et al., 2014
The section “Neural basis of inflammation-induced fatigue” links fatigue to impaired norepinephrine transmission and describes inflammation-related changes in dopamine and serotonin transmission (page unavailable). It identifies brainstem catecholaminergic projections, but does not establish that projections for all three monoamines are impaired or that availability of all three is reduced at cortical and subcortical targets. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAcute infectious illnesses cause CNS responses such as fever and common sickness symptoms including fatigue, sleepiness, social withdrawal, negative mood, pain hypersensitivity, and decreased appetite.
“acute infectious illnesses cause CNS responses such as fever (230) and a set of common symptoms of sickness, including fatigue, sleepiness, social withdrawal, negative mood (depression, anxiety), pain hypersensitivity, and decreased appetite (131).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [131]
Fever and sickness behavior in response to infection or inflammatory diseases are mediated by inflammatory mediators, including cytokines and prostaglandins that signal to the brain.
“fever and sickness behavior in response to infection or inflammatory diseases are mediated by inflammatory mediators, including cytokines and PGs that signal to the brain (131, 487).”
From The Sleep-Immune Crosstalk in Health and Disease (2019) · cites this paper as [131]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 88 · Cited by 346
- Authors
- Dantzer, R., Heijnen, C. J., Kavelaars, A., Laye, S., & Capuron, L.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Université de Bordeaux (FR)
- Corresponding author
- Dantzer, Robert
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 37
- Issue
- 1
- Pages
- 39-46
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC3889707
- OpenAlex
- W2054613715
- Cited by
- 346
- References
- 88
- Citations by year
- 2026: 24 · 2025: 29 · 2024: 30 · 2023: 40 · 2022: 40 · 2021: 30 · 2020: 28 · 2019: 27 · 2018: 26 · 2017: 14 · 2016: 32 · 2015: 21 · 2014: 5
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion)
- Funders
- National Institutes of Health (RO1NS074999)
- National Cancer Institute (P30CA016672)
- National Institute of Neurological Disorders and Stroke (R01NS074999, R01NS073939)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- fatigue, neuroimmune interactions, inflammatory mediators, innate immune activation, neurotransmitter metabolism, neurotoxicity, neurotrophic factors, fronto-striatal network, insula, interoception, incentive motivation, behavioral flexibility, central nervous system
- MeSH terms
- Animals, Fatigue, Humans, Neuroimmunomodulation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
