Interferon-γ and nitric oxide production during Behçet uveitis: immunomodulatory effect of interleukin-10.

Uveitis is one of the major manifestations of Behçet Disease, a systemic inflammatory vasculitis. Our aim is to investigate in vivo and in vitro production of interferon (IFN)-γ and nitric oxide (NO) during Behçet uveitis (BU). Moreover, we evaluated the implication of IFN-γ and interleukin (IL)-10 in the regulation of NO production in vitro. Cytokines' concentrations were measured by ELISA, and NO levels were assessed by modified Griess's method. Our results showed that patients with active disease had significant elevation of IFN-γ and NO concentrations in both plasma and peripheral blood mononuclear cell culture supernatants compared with controls (P<0.01) or to patients with inactive disease (P<0.05). Further, IFN-γ induced significantly higher production of NO in cell culture supernatants, whereas IL-10 significantly reduced it (P<0.05). In conclusion, the elevated levels of IFN-γ in vivo and in vitro in patients with BU reflect the implication of this cytokine in the disease physiopathology. These results suggest that IFN-γ, through the induction of NO synthase 2 and the production of NO, is implicated in the genesis of the inflammatory process during active BU; whereas IL-10 seems to have protective properties.

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-γ (IFN-γ) 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-γ and nitric oxide (NO) in bowel disease pathogenesis. In this study, we investigated the circulating IFN-γ 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-γ on NO production by peripheral blood mononuclear cells (PBMCs) of these patients. Our results indicate that IFN-γ/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-γ and NO production in IBD patients were confirmed by in vitro experiments and the role of IFN-γ in NO synthase induction in patients' PBMC culture was suggested. Collectively, our results show that IFN-γ plays a pivotal role in IBD pathogenesis through NO pathway.