Background: Pouchitis has been suggested to be a recurrence of ulcerative colitis in a colon‐like mucosa. Topical steroids are a valid therapeutic alternative for distal forms of ulcerative colitis. Aim: To investigate the efficacy and tolerability of budesonide enema in the treatment of pouchitis compared with oral metronidazole. Materials and methods: Twenty‐six patients with an active episode of pouchitis (defined as a pouchitis disease activity index score ≥ 7) and no treatment during the previous month were randomized to receive either budesonide enema (2 mg/100 mL at bedtime) plus placebo tablets or oral metronidazole (0.5 g b.d.) plus placebo enema in a prospective, double‐blind, double‐dummy, 6‐week, controlled trial. Results: Based on the intention‐to‐treat principle, we detected a significant improvement in disease activity at the end of the first week with both drugs (P < 0.01). After that, improvement was moderated until stabilization at 4 weeks in both treatments. The per protocol analysis showed that both drugs had similar efficacy in terms of disease activity, clinical and endoscopic findings. Fifty‐eight per cent and 50% of patients improved (decrease in pouchitis disease activity index ≥ 3) with budesonide enema and metronidazole, respectively (odds ratio, 1.4; confidence interval, 0.2–8.9). Adverse effects were observed in 57% of patients given metronidazole and in 25% of patients given budesonide. Conclusions: Budesonide enemas are an alternative treatment for active pouchitis, with similar efficacy but better tolerability than oral metronidazole.

Objective: To investigate serum levels of transforming growth factor‐β1 and interferon‐γ in active ulcerative colitis and to assess changes during treatment. Methods: We prospectively evaluated serum from 25 patients with untreated active ulcerative colitis and 19 healthy controls. Disease activity score (DAI), serum transforming growth factor‐β1 and interferon‐γ levels were measured at baseline and after 7 days of conventional treatment. Disease activity score and transforming growth factor‐β1 were also assessed at 42 days. Results: Baseline transforming growth factor‐β1 levels were significantly higher in patients than in controls (P < 0.02). On the 7th day, transforming growth factor‐β1 levels increased only in patients who responded (P < 0.01); variations in transforming growth factor‐β1 levels and disease activity score were inversely correlated (r=– 0.72, P < 0.001). At day 42, serum transforming growth factor‐β1 decreased significantly compared with the 7th day (P < 0.05). While in controls, interferon‐γ was undetectable; untreated patients had higher, widely variable, levels. At day 7, responders had higher interferon‐γ values than unresponsive cases. Variations in interferon‐γ correlated moderately with changes in transforming growth factor‐β1 (r=0.53, P < 0.05). Cytokine response did not depend upon the type of treatment. Conclusions: Both transforming growth factor‐β1 and interferon‐γ may play a role in the injury–repair process in active ulcerative colitis. Variations in circulating transforming growth factor‐β1 levels in the first week of treatment seem to be related to the therapeutic response.

Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.

Diverse immunoregulatory circuits operate to preserve intestinal homeostasis and prevent inflammation. Galectin-1 (Gal1), a β-galactoside–binding protein, promotes homeostasis by reprogramming innate and adaptive immunity. Here, we identify a glycosylation-dependent “on-off” circuit driven by Gal1 and its glycosylated ligands that controls intestinal immunopathology by targeting activated CD8+ T cells and shaping the cytokine profile. In patients with inflammatory bowel disease (IBD), augmented Gal1 was associated with dysregulated expression of core 2 β6-N-acetylglucosaminyltransferase 1 (C2GNT1) and α(2,6)-sialyltransferase 1 (ST6GAL1), glycosyltransferases responsible for creating or masking Gal1 ligands. Mice lacking Gal1 exhibited exacerbated colitis and augmented mucosal CD8+ T cell activation in response to 2,4,6-trinitrobenzenesulfonic acid; this phenotype was partially ameliorated by treatment with recombinant Gal1. While C2gnt1−/− mice exhibited aggravated colitis, St6gal1−/− mice showed attenuated inflammation. These effects were associated with intrinsic T cell glycosylation. Thus, Gal1 and its glycosylated ligands act to preserve intestinal homeostasis by recalibrating T cell immunity.

No abstract