Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?
OBJECTIVE
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 (deltaACTH) and the IL-6 levels. A similar relationship existed between the deltaACTH/deltacortisol 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.
Dinan
Timothy G
TG
Alimentary Pharmabiotic Centre, University College Cork, Ireland. t.dinan@ucc.ie
Quigley
Eamonn M M
EM
Ahmed
Salah M M
SM
Scully
Paul
P
O'Brien
Sinead
S
O'Mahony
Liam
L
O'Mahony
Siobhan
S
Shanahan
Fergus
F
Keeling
P W Napoleon
PW
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000428:Alcohol Drinking; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D003907:Dexamethasone; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D007422:Intestines / Q000503:physiopathology*; D007494:Ireland; D043183:Irritable Bowel Syndrome / Q000097:blood / Q000503:physiopathology*; D008297:Male; D010146:Pain; D012016:Reference Values
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D016753:Interleukin-10; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone