Hypothalamic-Pituitary-Gut Axis Dysregulation in Irritable Bowel Syndrome: Plasma Cytokines as a Potential Biomarker?

Dinan, Timothy G.; Quigley, Eamonn Martin; Ahmed, Salah M M; Scully, Paul; O’Brien, Sarah; O’Mahony, Liam; O’Mahony, Siobhain M.; Shanahan, Fergus; Keeling, P. W. N.

doi:10.1053/j.gastro.2005.11.033

Cited by 552 publications

(469 citation statements)

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“…However, it is well established that altered central processing of visceral pain plays a key role in IBS (Mayer et al 2009), and we have recently provided evidence that IBS is associated with a deficit in hippocampal-mediated cognitive function (Kennedy et al 2013). Thus, when considering our results along with previous pharmacological challenge tests (Dinan et al 2006) and a recent study describing elevated cortisol levels in anticipation of a public-speaking task (Heitkemper et al 2012), it is likely that HPA axis dysfunction in IBS is best characterized as an exaggerated response, or sustained activation following acute stress, which may, in part, be mediated by altered central processing of the stressful environment.…”

Section: Discussionmentioning

confidence: 59%

A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

et al. 2014

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Background. Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS.Method. Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre-and post-exposure to the TSST.Results. The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUC G ) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups.Conclusions. Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

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Section: Discussionmentioning

confidence: 59%

A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

et al. 2014

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“…Cytokine assays have revealed no major changes in the basal levels of cytokines in IBS patients [31][32][33][34] with the exception of IL6 and IL8, which have been found to be moderately increased in some studies. 31,34,35 A decrease in the levels of the antiinflammatory cytokine IL10 has also recently been reported in children with IBS, 36 although this decrease was not observed in adults. 31,32 However, several studies that assessed the effect of immune challenges on cytokine production by peripheral blood mononuclear cells isolated from IBS patients have reported the abnormal secretion of both pro-and anti-inflammatory cytokines.…”

Section: Resultsmentioning

confidence: 97%

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Matricon

Méleine

Gelot

et al. 2012

Aliment Pharmacol Ther

187

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This uncommissioned review article was subject to full peer-review. SUMMARY BackgroundIrritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. AimTo determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. MethodsThe scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. ResultsImmune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. ConclusionsThe changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

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“…Corticotropin-releasing factor (CRF) is a neuromodulator involved in the behavioral and physiological response to stress and is often linked to adversity associated with anxiety and pain disorders, including irritable bowel syndrome (IBS; Chang et al, 2009;Dinan et al, 2006;Fukudo, 2013). In support, our previous studies and others have investigated the effects of repeated psychological stress in a preclinical model that reproduces the hallmark traits of IBS (Bradesi et al, 2005;Myers and Greenwood-Van Meerveld, 2012;Tran et al, 2013;Venkova et al, 2010).…”

Section: Introductionmentioning

confidence: 93%

Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain

Tran

Schulkin

Meerveld

2014

Neuropsychopharmacol

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Corticotropin-releasing factor (CRF)-mediated mechanisms in the bed nucleus of the stria terminalis (BNST) have a pivotal role in stressinduced anxiety and hyperalgesia. Although CRF is known to activate two receptor subtypes, CRF 1 and CRF 2 , attempts to delineate the specific role of each subtype in modulating anxiety and nociception have been inconsistent. Here we test the hypothesis that CRF 1 and CRF 2 receptor activation in the anteriolateral BNST (BNST AL ) facilitates divergent mechanisms modulating comorbid anxiety and hyperalgesia. Microinfusions of the specific antagonists CP376395 and Astressin 2 B into the BNST AL were used to investigate CRF 1 and CRF 2 receptor functions, respectively. We found that CRF 1 and CRF 2 receptors in the BNST AL had opposing effects on exploratory behavior in the elevated plus-maze, somatic mechanical threshold, and the autonomic and endocrine response to stress. However, CRF 1 or CRF 2 receptor antagonism in the BNST AL revealed complementary roles in facilitating the acoustic startle and visceromotor reflexes. Our results suggest that the net effect of CRF 1 and CRF 2 receptor activation in the BNST AL is pathway-dependent and provides important insight into the CRF receptor-associated circuitry that likely underpins stress-induced pathologies.

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Hypothalamic-Pituitary-Gut Axis Dysregulation in Irritable Bowel Syndrome: Plasma Cytokines as a Potential Biomarker?

Cited by 552 publications

References 40 publications

A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

A sustained hypothalamic–pituitary–adrenal axis response to acute psychosocial stress in irritable bowel syndrome

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

Importance of CRF Receptor-Mediated Mechanisms of the Bed Nucleus of the Stria Terminalis in the Processing of Anxiety and Pain

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