Sensory neuro-immune interactions differ between Irritable Bowel Syndrome subtypes

Hughes, Patrick A.; Harrington, Andrea M.; Castro, Joel; Liebregts, Tobias; Adam, Birgit; Grasby, Dallas J.; Isaacs, Nicole J.; Maldeniya, Lochana; Martin, C. M.; Persson, Jenny; Andrews, Jane M.; Holtmann, Gerald; Blackshaw, L. Ashley; Brierley, Stuart M.

doi:10.1136/gutjnl-2011-301856

Cited by 184 publications

(248 citation statements)

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“…PBMC were isolated from fresh blood by density centrifugation as previously described (Hughes et al, 2013a;Liebregts et al, 2007). Briefly, fresh blood was 11 diluted 1:2 in PBS, layered onto Lymphoprep solution (Lymphoprep, Axis Shield, Norway) and centrifuged at 850g for 20 min.…”

Section: Peripheral Blood Mononuclear Cell Isolation and Culturementioning

confidence: 99%

“…Colo-rectal single unit extracellular electrophysiological recordings from muscular / mucosal afferents from the pelvic nerve were performed as previously described (Brierley et al, 2009;Brierley et al, 2004;Brierley et al, 2008;Hughes et al, 2009b;Hughes et al, 2013a). Briefly the distal colo-rectum plus attached pelvic nerves were removed from the mice, the colo-rectum opened up longitudinally and pinned mucosal side up in a specialized organ bath.…”

Section: Electrophysiologymentioning

confidence: 99%

“…However, the generation and propagation of action potentials is a dynamic process that not only results from increased excitation, but also loss of inhibition. We recently showed that muscular / mucosal afferent electrophysiological responses to distension were inhibited following incubation with unstimulated peripheral blood mononuclear cell (PBMC) supernatants from healthy subjects in a manner consistent with activation of the µ-opioid receptor (MOR) (Hughes et al, 2009c;Hughes et al, 2013a). This inhibition was lost following incubation with supernatants from IBS-C patients and switched to sensitization after incubation with supernatants from IBS-D, an effect we characterized as cytokine driven (Hughes et al, 2009c;Hughes et al, 2013a).…”

Section: Introductionmentioning

confidence: 97%

“…Cohort 1 Blood was taken from 35 IBS patients (58% female; median age 46.3 yr 15 IBS-D, 20 IBS-C) and from 36 HS (63% female; median age 38.9 yr) as previously described (Hughes et al, 2013a;Liebregts et al, 2007). PBMC supernatants (see below) from this cohort were used for electrophysiology experiments.…”

Section: Introductionmentioning

confidence: 99%

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients, Brain, Behavior, and Immunity (2014), doi: http://dx.doi.org/10. 1016/j.bbi.2014.07.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. supernatants from HS and IBS patients were applied to colo-rectal sensory afferent endings in mice with post-inflammatory chronic visceral hypersensitivity (CVH). β-endorphin was identified predominantly in monocyte / macrophages relative to T or B cells in human PBMC and colonic lamina propria. Monocyte derived β-endorphin levels and colonic macrophage numbers were lower in IBS patients than healthy subjects. PBMC supernatants from healthy subjects had greater inhibitory effects on colo-rectal afferent mechanosensitivity than those from IBS patients. The inhibitory effects of PBMC supernatants were more prominent in CVH mice compared to healthy mice due to an increase in µ-opioid receptor expression in dorsal root ganglia neurons in CVH mice. Monocyte / macrophages are the predominant immune cell type responsible for β-endorphin secretion in humans. IBS patients have lower monocyte derived β-endorphin levels than healthy subjects, causing less inhibition of colonic afferent endings. Consequently, altered immune function contributes toward visceral hypersensitivity in IBS.

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Section: Peripheral Blood Mononuclear Cell Isolation and Culturementioning

confidence: 99%

Section: Electrophysiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Hughes

Moretta

Lim

et al. 2014

Brain, Behavior, and Immunity

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“…Th e work of Valdez-Morales does, however, add support to the notion that IBS-D is a distinctive entity where immune activation and impaired epithelial integrity are common features (14,15,19,38) where mechanisms of pain generation may be diff erent ( 4 ) to IBS-C. Indeed, proteases may be the mediators of both barrier dysfunction and visceral sensitivity in this subgroup ( 39 ).…”

mentioning

confidence: 80%

Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

Quigley

2013

American Journal of Gastroenterology

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Although the etiology of irritable bowel syndrome (IBS) remains unknown, clinical and laboratory observations suggest that within the broad and varying phenotype, that is, IBS, there may exist subgroups, which can be defi ned on the basis of a distinctive pathophysiological basis. Of these, postinfectious IBS is the best characterized; in IBS, in general, studies of infl ammatory mediators and substances elaborated by cells involved in the intestinal immune response, such as proteases, suggest that some IBS sufferers can be differentiated on the basis of an aberrant immune response. Valdez-Morales and colleagues extend this concept by demonstrating the ability of supernatants of biopsy cultures from individuals with diarrheapredominant IBS to enhance neuronal excitabilityan effect that could well contribute to a clinical hallmark of IBS, namely, visceral hypersensitivity. Am J Gastroenterol 2013; 108:1644 -1646 doi: 10.1038/ajg.2013 Irritable bowel syndrome (IBS) is a common and, at times, disabling condition whose etiology, despite the best eff orts of clinicians and scientists, remains unclear. As a consequence, reliable biomarkers for the syndrome have yet to emerge, and its diagnosis, therefore, continues to rest on clinical features and the exclusion of disorders that have the potential to present in a similar manner ( 1 ). Much of the diffi culties related to unraveling the enigma that is IBS revolve around its heterogeneity, which may originate from any one or a combination of the following: dominant symptom (pain, discomfort, bloating, distension, and altered bowel habit), predominant bowel habit (diarrhea, constipation, or mixed pattern), comorbidity (be it psychological or somatic), severity (including impact on the quality of life), natural history, and prognosis. To frustrate the clinician scientist further, those IBS subtypes that can be defi ned with some degree of accuracy, at least using Rome III criteria (2), including diarrhea-predominant IBS, constipationpredominant IBS and mixed IBS, do not appear to be immutable, and suff erers can move from one stool pattern to another over time, thus emphasizing the importance of longitudinal studies of this disorder ( 3,4 ).However, in this rather gloomy scenario, shines an unexpected beam of light that has illuminated (or, to be accurate, reignited) a new perspective on the etiology of IBS -postinfectious IBS (PI-IBS) ( 5 ). Although PI-IBS had been well described decades beforehand ( 6 ), more recent studies based on the consequences of large-scale outbreaks of bacterial, viral, and amebic gastroenteritis have firmly brought the concept of host -microbiome interactions into play in IBS research, in general ( 7 ). Observations in relation to PI-IBS, such as the description of correlations between the initial inflammatory response to the infection and the subsequent development of IBS ( 8 ), as well as the identification of polymorphisms in genes coding for components of the mucosal immune response and intestinal barrier integrity as risk factor...

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Mu and delta opioid receptor knockout mice show increased colonic sensitivity

Reiss

Ceredig

Sécher

et al. 2016

European Journal of Pain

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Sensory neuro-immune interactions differ between Irritable Bowel Syndrome subtypes

Abstract: Distinct patterns of immune dysfunction and interaction with sensory pathways occur in different patient groups and through different intracellular pathways. Our results indicate IBS patient subgroups would benefit from selective targeting of the immune system.

Cited by 184 publications

References 53 publications

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients

Editorial: PARs for the Course: Roles of Proteases and PAR Receptors in Subtly Inflamed Irritable Bowel Syndrome

Mu and delta opioid receptor knockout mice show increased colonic sensitivity

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