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Uncoupling between the vagal tone and HPA axis in patients with Crohn's disease or irritable bowel syndrome: Relation to stress and inflammation

      The aim of this work was to study the functional coupling between vagal tone, cortisol, inflammatory cytokines and emotions in patients with Crohn's disease (CD) or irritable bowel syndrome (IBS) compared to healthy subjects. The study was performed in 76 subjects (27 healthy subjects, 27 CD patients in remission, 30 IBS patients). The parasympathetic vagal tone was evaluated by the high frequency band of heart rate variability. On their arrival at laboratory (8:00 AM), subjects completed questionnaires for anxiety and depressive symptoms and were then equipped with electrodes for electrocardiogram (ECG) and a venous catheter. After a resting period of 60 min, ECG was recorded for 10 min. Salivary cortisol was measured the day before at 8:00 AM and 10:00 PM. Catecholamines and pro-inflammatory cytokines (TNF-alpha, IL1, and IL6) were measured in blood samples taken at the end of the resting ECG. A significant interaction between vagal tone and pathology was found for cortisol, adrenaline and TNF-alpha. In healthy subjects, the vesperal level of salivary cortisol was inversely correlated (r = −0.38, p = 0.06) with vagal tone while this correlation was not observed in CD and IBS patients. An inverse relationship between vagal tone and TNF-alpha plasma concentration was observed in CD (r = −0.45; p = 0.04) while vagal tone was inversely correlated with plasma adrenaline in IBS (r = −0.43, p = 0.02). In addition, adrenaline was related to anxiety scores (r = 0.25, p = 0.02) and depressive symptomatology (r = 0.29, p = 0.009). These results reveal an uncoupling between the HPA axis and vagal tone in CD and IBS and a correlation between vagal tone and TNF-alpha in CD and between vagal tone and adrenaline in IBS. This highlights the relevance of therapies focused on vagus nerve and emotional regulation in these diseases.
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