Activation of signal transducer and activator of transcription-1 (STAT-1) and differential expression of interferon-γ and anti-inflammatory proteins in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis

Abstract

Summary: Pouchitis after total rectocolectomy is the most common complication of ulcerative colitis (UC). The immunological mechanisms involved in the genesis of pouchitis are unclear. Therefore, we evaluated the inflammatory activity in normal ileal pouch mucosa by determining signal transducers and activators of transcription (STAT-1) activation and cytokine expression in patients operated for UC and familial adenomatous polyposis (FAP). Eighteen asymptomatic patients, who underwent total rectocolectomy and J pouch, were evaluated: nine with UC and nine with FAP. The activation of STAT-1 and cytokine expression were determined by immunoblot of total protein extracts from pouch mucosal biopsies. The absence of pouchitis was assessed by clinical, histological and endoscopic parameters, according to the Pouchitis Disease Activity Index. The patients were not receiving any medication. Analysis of variance (anova) and Tukey–Kramer's test were applied. The local ethical committee approved the study and informed consent was signed by all participants. STAT-1 activation was increased in UC when compared to FAP and controls (P < 0·05). Higher levels of interferon (IFN)-γ expression were observed in UC patients when compared to the control group (P < 0·05), but were similar to FAP. In contrast, cytokine signalling (SOCS-3) and interleukin (IL)-10 expression were similar in all groups (P > 0·05). These findings could explain the higher susceptibility to this inflammatory complication in UC when compared to FAP. A tendency towards increased levels of IFN-γ and STAT-1 in patients with UC, even without clinical and endoscopic evidence of pouchitis, was observed; studying inflammatory activity in asymptomatic ileal pouches may help understanding of the pathogenesis of pouchitis.