Lack of macrophage/monocyte derived β-endorphin contributes toward sensations of pain/discomfort in Irritable Bowel Syndrome (P3153)

Abstract Introduction: Neuroimmune interactions are increasingly implicated in Irritable Bowel Syndrome (IBS). Immune derived β-endorphin (β-end) inhibits colonic sensory afferents in health (Hughes et. al. Gut 2012), but little is known of the immunocyte responsible for β-end secretion in humans and whether this is altered in IBS patients. Methods: β-end and TNF-α staining was assessed by flow cytometry analysis of CD4, CD8, CD19, CD14 or CD33 labelled PBMC that were unstimulated or stimulated with PMA/ionomycin or LPS and compared between 9 healthy and 21 IBS patients. β-end immunoreactivity was assessed in CD3 or CD68 labelled colonic biopsies from 7 healthy and 10 IBS patients. Results: In PBMC β-end was observed in unstimulated monocytes and LPS stimulated macrophages, but not unstimulated or PMA/ionomycin stimulated T or B cells, and was decreased in IBS patients relative to healthy subjects. Most β-end stained cells in colonic biopsies were CD68 positive, while only a low proportion were CD3 positive, and IBS patients had decreased numbers of CD68+ve cells. Intracellular levels of β-end negatively correlated with TNF-α in monocytes, and positively correlated with macrophage numbers in colonic biopsies. Discussion: Monocyte / macrophages are the predominant immune derived source of β-end in human subjects, and this is lower in IBS patients. The loss of immune derived β-end potentially contributes toward the sensations of pain / discomfort in IBS.