The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis

Abstract

Background: Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed. Aim: To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction. Methods: This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined. Results: Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γhad a significantly higher incidence of pouchitis compared with low IFN-γpatients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γexpression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γmessenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03). Conclusion: IFN-γexpression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.