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Cited by 212Vagus Nerve Stimulation ResearchHeart Rate Variability and Autonomic ControlInflammatory Bowel Disease

Relationship between Vagal Tone, Cortisol, TNF-Alpha, Epinephrine and Negative Affects in Crohn’s Disease and Irritable Bowel Syndrome

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Pellissier, Sonia, Dantzer, Cécile, Mondillon, Laurie, Trocme, Candice, Gauchez, Anne-Sophie, Ducros, Véronique, Mathieu, Nicolas, Toussaint, Bertrand +3 more·2014·PLoS ONE
DOI 10.1371/journal.pone.0105328PMC PMC4160179
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Abstract

Crohn's disease (CD) and irritable bowel syndrome (IBS) involve brain-gut dysfunctions where vagus nerve is an important component. The aim of this work was to study the association between vagal tone and markers of stress and inflammation in patients with CD or IBS compared to healthy subjects (controls). The study was performed in 73 subjects (26 controls, 21 CD in remission and 26 IBS patients). The day prior to the experiment, salivary cortisol was measured at 8:00 AM and 10:00 PM. The day of the experiment, subjects completed questionnaires for anxiety (STAI) and depressive symptoms (CES-D). After 30 min of rest, ECG was recorded for heart rate variability (HRV) analysis. Plasma cortisol, epinephrine, norepinephrine, TNF-alpha and IL-6 were measured in blood samples taken at the end of ECG recording. Compared with controls, CD and IBS patients had higher scores of state-anxiety and depressive symptomatology. A subgroup classification based on HRV-normalized high frequency band (HFnu) as a marker of vagal tone, showed that control subjects with high vagal tone had significantly lower evening salivary cortisol levels than subjects with low vagal tone. Such an effect was not observed in CD and IBS patients. Moreover, an inverse association (r = -0.48; p<0.05) was observed between the vagal tone and TNF-alpha level in CD patients exclusively. In contrast, in IBS patients, vagal tone was inversely correlated with plasma epinephrine (r = -0.39; p<0.05). No relationship was observed between vagal tone and IL-6, norepinephrine or negative affects (anxiety and depressive symptomatology) in any group. In conclusion, these data argue for an imbalance between the hypothalamus-pituitary-adrenal axis and the vagal tone in CD and IBS patients. Furthermore, they highlight the specific homeostatic link between vagal tone and TNF-alpha in CD and epinephrine in IBS and argue for the relevance of vagus nerve reinforcement interventions in those diseases.

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  • In Crohn's disease, individuals with low parasympathetic activity (HFnu) had significantly greater tumor necrosis factor-α levels compared with IBS and HC groups.

    “individuals in the CD group with low parasympathetic activity had significantly greater tumor necrosis factor-α levels compared with IBS and HC groups.”

    From Alterations in Heart Rate Variability Associated With Irritable Bowel Syndrome or Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis (2021) · cites this paper as [44]

    The Results section (“Vagal tone and pro-inflammatory cytokines”; page not provided) reports significantly higher TNF-α in low- than high-parasympathetic-tone Crohn’s patients. It does not report a significant TNF-α comparison between those Crohn’s patients and the IBS or healthy-control groups; it says only that the tone–TNF-α relationship was not observed in those groups. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • When categorized into high parasympathetic activity, there were no differences in tumor necrosis factor-α levels between CD, IBS, or HC groups.

    “When categorized into high parasympathetic activity; however, there were no differences in tumor necrosis factor-α levels between CD, IBS, or HC groups (44).”

    From Alterations in Heart Rate Variability Associated With Irritable Bowel Syndrome or Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis (2021) · cites this paper as [44]

    The Results section, “Vagal tone and pro-inflammatory cytokines” (page unavailable), compares TNF-α levels between high- and low-parasympathetic-tone subgroups within each group. It does not report whether TNF-α levels differ among the high-tone CD, IBS, and healthy-control groups; searches for that cross-group comparison found no passage addressing it. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Pellissier, S., Dantzer, C., Mondillon, L., Trocme, C., Gauchez, A.-S., Ducros, V., Mathieu, N., Toussaint, B., Fournier, A., Canini, F., & Bonaz, B.
Affiliations
  • Laboratoire Inter-universitaire de Psychologie: Personnalité, Cognition, Changement Social (FR)
  • Centre National de la Recherche Scientifique (FR)
  • Centre Hospitalier Universitaire de Grenoble (FR)
  • Université Joseph Fourier (FR)
  • Inserm (FR)
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-09-10
Volume
9
Issue
9
Pages
e105328
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0105328
PMC
PMC4160179
OpenAlex
W1982056870
Cited by
212
References
73
Citations by year
2026: 16 · 2025: 22 · 2024: 17 · 2023: 21 · 2022: 16 · 2021: 24 · 2020: 20 · 2019: 17 · 2018: 14 · 2017: 13 · 2016: 21 · 2015: 9 · 2012: 2
FWCI
7.46
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by)
Funders
Société Nationale Française de Gastro-Entérologie
Topics
  • Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
Crohn's disease, irritable bowel syndrome, vagal tone, heart rate variability, salivary cortisol, epinephrine, TNF-α, interleukin-6, norepinephrine, anxiety, depressive symptoms, hypothalamic-pituitary-adrenal axis, gut-brain axis, vagus nerve, inflammation
MeSH terms
Adolescent, Adult, Crohn Disease, Epinephrine, Female, Heart Rate, Humans, Hydrocortisone, Male, Middle Aged, Norepinephrine, Saliva, Tumor Necrosis Factor-alpha, Vagus Nerve, Interleukin-6, Cluster Analysis, Case-Control Studies, Irritable Bowel Syndrome, Young Adult

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