P059 Cigarette smoke improves colonic inflammation through NKT cells activation in mice

Background: Mechanisms triggering the early lesions of Crohn’s Disease (CD) aren’t fully understood. Endoscopic recurrence (ER) after surgery is one of the best situations for studying the pathogenesis of initial lesion of CD. Aim of the study was to examine the profiles of cytokines produced in the neoterminal ileo of CD pts after curative ileo-colonic resection. Methods: Mucosal biopsies were obtained from CD pts underwent ileocolonoscopy within 12 mos after ileocolectomy. Additional mucosal samples taken from intestinal resection specimens of CD pts undergoing intestinal resection for a chronic active disease were considered as established lesion. Normal controls (ctr) included ileal biopsies from pts undergoing ileocolonoscopy for irritable bowel syndrome. ER was evaluated and scored according to the criteria of Rutgeerts. RNA transcripts were analyzed in biopsies from CD pts and controls by real-time PCR. Lamina propria mononuclear cells were isolated from mucosal samples and analyzed for cytokines and FoxP3 expression by flow-cytometry. Results: No ER is seen in 8 out of 19 pts defined as Rutgeerts i0, while the remaining 11 pts as ER (i2 to i4). CD mucosa of the neoterminal ileo, independently of ER, and in CD established lesion is infiltrated with high numbers of CD3+ cells as compared to ctr, CD3+ cells are more pronounced in established lesion compared to the neoterminal ileo. TNFalpha is highly expressed in the neoterminal ileo independently of ER but not in the established lesions as compared to ctr; by contrast, up regulation of IFN-gamma and IL-21 is seen in the neoterminal ileo independently of the presence of ER and in the established lesion compared to ctr. IL-17A, IL-6 and IL-4 are more pronounced in the established lesion and in the neoterminal ileo in presence of ER in comparison to the unaffected neoterminal ileo and ctr. Foxp3 expression is increased in areas with mucosal lesions but not in the unaffected neoterminal ileo compared to ctr. Conclusions: Distinct profiles of cytokines are produced during the early and established phases of CD. Even in the absence of ER, the neoterminal ileo exhibits enhanced synthesis of inflammatory cytokines. Blockade of such cytokines could be useful for preventing ER.