Involvement of Interferon-γ in Bowel Disease Pathogenesis by Nitric Oxide Pathway: A Study in Algerian Patients

The pathogenesis of inflammatory bowel disease (IBD) is complex, involving a wide range of molecules including cytokines. Abnormalities in the expression of immunoregulatory cytokines such as interferon-gamma (IFN-gamma) and interleukin-12 (IL-12) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. The aim of this work was to study the implication of IFN-gamma and nitric oxide (NO) in bowel disease pathogenesis. In this study, we investigated the circulating IFN-gamma and IL-12 production in 2 groups of Algerian patients with IBD (Crohn's disease and ulcerative colitis). Moreover, systemic NO concentrations and NO generation by colonic mucosa were determined in these patients. Finally, we examined the effect of IFN-gamma on NO production by peripheral blood mononuclear cells (PBMCs) of these patients. Our results indicate that IFN-gamma/IL-12 production in IBD patients was increased in comparison to healthy donors. This strong production correlates with high levels of NO in sera and colonic mucosa culture. Interestingly, NO production was related to the clinical stage of IBD patients (inactive or active stage). The relationship between IFN-gamma and NO production in IBD patients were confirmed by in vitro experiments and the role of IFN-gamma in NO synthase induction in patients' PBMC culture was suggested. Collectively, our results show that IFN-gamma plays a pivotal role in IBD pathogenesis through NO pathway.