TY - JOUR
T1 - Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome
T2 - Plasma cytokines as a potential biomarker?
AU - Dinan, Timothy G.
AU - Quigley, Eamonn M.M.
AU - Ahmed, Salah M.M.
AU - Scully, Paul
AU - O'Brien, Sinead
AU - O'Mahony, Liam
AU - O'Mahony, Siobhan
AU - Shanahan, Fergus
AU - Keeling, P. W.Napoleon
N1 - Funding Information:
Supported in part by Science Foundation Ireland in the form of a centre grant (Alimentary Pharmabiotic Centre), the Health Research Board of Ireland, the Higher Education Authority of Ireland, and the Wellcome Trust.
PY - 2006/2
Y1 - 2006/2
N2 - Background & Aims: Irritable bowel syndrome (IBS) is a functional disorder with an etiology that has been linked to both psychological stress and infection. The primary aim of this study was to examine the hypothalamic- pituitary-adrenal axis in patients with IBS and to relate such response to plasma cytokine profiles. Methods: A total of 151 subjects, 76 patients and 75 controls, were recruited. The patients with IBS were diagnosed according to Rome II criteria. Forty-nine patients and 48 matched controls had cytokine levels measured, and a subset of 21 patients and 21 controls also underwent a corticotropin-releasing hormone (CRH) stimulation test with plasma levels of adrenocorticotropic hormone (ACTH) and cortisol measured. The remaining 27 patients and 27 controls underwent a dexamethasone (1 mg) challenge. Results: Cortisol and the proinflammatory cytokines interleukin (IL)-6 (together with its soluble receptor) and IL-8 were elevated in all IBS subgroups (diarrhea predominant, constipated, and alternators), although the elevation was most marked in the constipated subgroup. There was no alteration in the anti-inflammatory cytokine IL-10. Following CRH infusion, an exaggerated release of both ACTH and cortisol was observed in patients with IBS. There was a significant correlation between the ACTH response (δACTH) and the IL-6 levels. A similar relationship existed between the δACTH/δcortisol ratio and the IL-6 levels. Dexamethasone suppression of cortisol was similar in patients and controls. Conclusions: IBS is characterized by an overactivation of the hypothalamic-pituitary-adrenal axis and a proinflammatory cytokine increase.
AB - Background & Aims: Irritable bowel syndrome (IBS) is a functional disorder with an etiology that has been linked to both psychological stress and infection. The primary aim of this study was to examine the hypothalamic- pituitary-adrenal axis in patients with IBS and to relate such response to plasma cytokine profiles. Methods: A total of 151 subjects, 76 patients and 75 controls, were recruited. The patients with IBS were diagnosed according to Rome II criteria. Forty-nine patients and 48 matched controls had cytokine levels measured, and a subset of 21 patients and 21 controls also underwent a corticotropin-releasing hormone (CRH) stimulation test with plasma levels of adrenocorticotropic hormone (ACTH) and cortisol measured. The remaining 27 patients and 27 controls underwent a dexamethasone (1 mg) challenge. Results: Cortisol and the proinflammatory cytokines interleukin (IL)-6 (together with its soluble receptor) and IL-8 were elevated in all IBS subgroups (diarrhea predominant, constipated, and alternators), although the elevation was most marked in the constipated subgroup. There was no alteration in the anti-inflammatory cytokine IL-10. Following CRH infusion, an exaggerated release of both ACTH and cortisol was observed in patients with IBS. There was a significant correlation between the ACTH response (δACTH) and the IL-6 levels. A similar relationship existed between the δACTH/δcortisol ratio and the IL-6 levels. Dexamethasone suppression of cortisol was similar in patients and controls. Conclusions: IBS is characterized by an overactivation of the hypothalamic-pituitary-adrenal axis and a proinflammatory cytokine increase.
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U2 - 10.1053/j.gastro.2005.11.033
DO - 10.1053/j.gastro.2005.11.033
M3 - Article
C2 - 16472586
AN - SCOPUS:32044459306
SN - 0016-5085
VL - 130
SP - 304
EP - 311
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -