Immune Activation in Patients With Irritable Bowel Syndrome

Liebregts, Tobias; Adam, Birgit; Bredack, Christoph; Röth, Alexander; Heinzel, Susanne; Lester, Sue; Downie-Doyle, Sarah; Smith, Eric; Drew, Paul A.; Talley, Nicholas J.; Holtmann, Gerald

doi:10.1053/j.gastro.2007.01.046

Cited by 572 publications

(544 citation statements)

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“…This suggestion is supported by previous reports demonstrating LPS stimulated PBMC from IBS patients secrete higher concentrations of macrophage derived cytokines including TNF-α, IL-1β and IL-6 relative to health (Hughes et al, 2013a;Liebregts et al, 2007;McKernan et al, 2011). As LPS is such a strong stimulator this type of response may be similar to that observed during overt inflammatory conditions, such as Inflammatory Bowel Disease (IBD).…”

supporting

confidence: 78%

“…Indeed infusions of up to 4 mg/kg/hr are reportedly well tolerated in healthy humans, although sensitivity to rectal distension at high doses is yet to be investigated (Clarke et al, 2005). Interestingly, our results suggest monocyte / macrophage derived β-endorphin levels do not differ between IBS patient cohorts, indicating the differences in the functional effects that supernatants from IBS-D and IBS-C patients have on colo-rectal sensory afferents are due to excitatory actions of cytokines TNF-α, IL-1β and IL-6, which we previously showed were increased in IBS-D relative to IBS-C (Hughes et al, 2013a;Liebregts et al, 2007). The lack of difference between patients based on bowel habit is perplexing however, as monocyte / macrophages are likely to be in close contact with the enteric nervous system where MOR agonists are well known to induce constipation.…”

Section: Discussionmentioning

confidence: 56%

“…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%

“…There was no evidence of a preceding gastrointestinal infection in IBS-C, IBS-A or healthy subjects (HS) in cohort 1 or in any subjects in cohort 2. Abdominal symptoms were assessed utilizing a validated self-report Bowel Disease Questionnaire before study participation (Liebregts et al, 2007). The ranked symptoms of pain intensity and pain frequency were pre-selected before data analysis.…”

Section: Introductionmentioning

confidence: 99%

“…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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supporting

confidence: 78%