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

Patrick Hughes, Melissa Moretta, Amanda Lim, Dallas Grasby, Daniel Bird, Stuart Brierley, Tobias Liebregts, Birgit Adam, Ashley Blackshaw, Gerald Holtmann, Peter Bampton, Peter Hoffmann, Jane Andrews, Heddy Zola, Doreen Krumbiegel

    Research output: Contribution to journalArticlepeer-review

    36 Citations (Scopus)

    Abstract

    Alterations in the neuro-immune axis contribute toward viscerosensory nerve sensitivity and symptoms in Irritable Bowel Syndrome (IBS). Inhibitory factors secreted from immune cells inhibit colo-rectal afferents in health, and loss of this inhibition may lead to hypersensitivity and symptoms. We aimed to determine the immune cell type(s) responsible for opioid secretion in humans and whether this is altered in patients with IBS. The β-endorphin content of specific immune cell lineages in peripheral blood and colonic mucosal biopsies were compared between healthy subjects (HS) and IBS patients. Peripheral blood mononuclear cell (PBMC) 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.

    Original languageEnglish
    Pages (from-to)191-203
    Number of pages13
    JournalBrain, Behavior, and Immunity
    Volume42
    DOIs
    Publication statusPublished - 1 Nov 2014

    Keywords

    • Irritable Bowel Syndrome
    • Macrophage
    • Monocyte
    • Neuro-immune
    • Opioid
    • Visceral pain

    Fingerprint

    Dive into the research topics of 'Immune derived opioidergic inhibition of viscerosensory afferents is decreased in Irritable Bowel Syndrome patients'. Together they form a unique fingerprint.

    Cite this