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

• Published in: PloS one Vol. 9; no. 9; p. e105328
• Main Authors: Pellissier, Sonia, Dantzer, Cécile, Mondillon, Laurie, Trocme, Candice, Gauchez, Anne-Sophie, Ducros, Véronique, Mathieu, Nicolas, Toussaint, Bertrand, Fournier, Alicia, Canini, Frédéric, Bonaz, Bruno
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.09.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Anxiety; Biology and Life Sciences; Brain; Case-Control Studies; Cluster Analysis; Cortisol; Crohn Disease - blood; Crohn Disease - metabolism; Crohn Disease - physiopathology; Crohn's disease; Echocardiography; EKG; Endocrinology and metabolism; Epinephrine; Epinephrine - blood; Female; Heart Rate; Human health and pathology; Humans; Hydrocortisone - blood; Hydrocortisone - metabolism; Hypothalamus; Hépatology and Gastroenterology; Immunology; Inflammatory bowel disease; Innate immunity; Interleukin 6; Interleukin-6 - blood; Intestine; Irritable bowel syndrome; Irritable Bowel Syndrome - blood; Irritable Bowel Syndrome - metabolism; Irritable Bowel Syndrome - physiopathology; Kinases; Life Sciences; Male; Medicine and Health Sciences; Mental depression; Middle Aged; Norepinephrine; Norepinephrine - blood; Pascal, Blaise (1623-1662); Patients; Pituitary; Psychiatrics and mental health; Remission; Rodents; Saliva - metabolism; Subgroups; Tumor Necrosis Factor-alpha - blood; Tumor necrosis factor-α; Vagus nerve; Vagus Nerve - physiopathology; Young Adult; France
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0105328

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.