Factors Associated with Poor Quality of Life in a Canadian Cohort of Patients with Inflammatory Bowel Disease: A Cross-sectional Study.

BACKGROUND: Health-related quality of life (QoL) is often adversely affected in patients with inflammatory bowel disease (IBD). We aimed to identify factors associated with poor QoL among Canadian patients with IBD in clinical remission. METHODS: We enrolled patients at a single academic tertiary care center with inactive IBD. All eligible patients completed a series of questionnaires that included questions on demographics, disease activity, anxiety, depression and the presence of irritable bowel syndrome (IBS) symptoms. Stool sample for fecal calprotectin (FC) was also collected to assess for subclinical inflammation. The primary outcome measure was QoL assessed by the short inflammatory bowel disease questionnaire (SIBDQ), with planned subgroup comparisons for fatigue, anxiety, depression and IBS symptoms. RESULTS: Ninety-three patients were eligible for inclusion in this study. The median SIBDQ scores were lower in patients with anxiety (P < 0.001), depression (P = 0.004), IBS symptoms (P < 0.001) and fatigue (P = 0.018). Elevated FC in patients in clinical remission did not impact QoL. These findings were consistent on multivariate linear regression. CONCLUSIONS: Anxiety, depression, fatigue and IBS symptoms are all independently associated with lower QoL in patients with inactive IBD. Clinicians are encouraged to screen for these important factors as they may detrimentally impact QoL in IBD patients even in clinical remission.

Lymphocyte-mediated regulation of beta-endorphin in the myenteric plexus.

Lymphocytes are antinociceptive and can modulate visceral pain perception in mice. Previously, we have shown that adoptive transfer of CD4+ T cells to severe combined immune-deficient (SCID) mice normalized immunodeficiency-related visceral hyperalgesia. Pain attenuation was associated with an increase in beta-endorphin release by T cells and an upregulation of beta-endorphin in the enteric nervous system. In this study, we investigated the relationship between T cells and opioid expression in the myenteric plexus. We examined opioid peptide and receptor expression in the myenteric plexus in the presence and absence of mucosal T cells. We found a positive association between T cells and beta-endorphin expression; this was accompanied by a downregulation of the micro-opioid receptor (MOR). In vitro, T helper (Th) type 1 and type 2 cytokine stimulation of CD4+ T cells or isolation of T cells from in vivo Th-polarized mice did not increase T cell release of beta-endorphin or the induction of beta-endorphin expression in the myenteric plexus. However, exogenous beta-endorphin did upregulate beta-endorphin expression, and both cycloheximide and naloxone methiodide inhibited peptide upregulation. Therefore, our results suggest that nonpolarized CD4+ T cells release beta-endorphin, which, through an interaction with MOR, stimulates an upregulation of beta-endorphin expression in the myenteric plexus. Thus, we propose that the mechanism underlying lymphocyte modulation of visceral pain involves T cell modulation of opioid expression in the enteric nervous system.