Cytokines and Nitric Oxide in Immunopathogenesis of IBD and Potential Therapeutic Approaches

Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a multi-factorial condition characterized by a chronic inflammation of the gastrointestinal tract. In IBD, the balance between pro/anti-inflammatory cytokines and immuno-regulatory cytokines is disturbed. An over-production of pro-inflammatory cytokines and nitric oxide characterizes the pathogenesis of IBD. In Crohn’s disease the major cytokines are generated by Th1and Th17-polarized T cells. In contract, UC is viewed more as an atypical Th2-type immune response characterized by the generation of high amount of IL-5, IL-4 and IL-13. Both Th1 and Th17 cytokines are involved in the up-regulation of iNOS expression in IBD and the production of high level of nitric oxide (NO). The latter, as an effect, causes tissue damages through the generation of reactive nitric oxygen species (RNOS). A better understanding of the pathogenesis of IBD has led to the development of new therapeutic strategies based on targeting cytokines and their receptors as well as NO modulation. Manipulation the microbiota with probiotics and helminthes may have potential use as anti-inflammatory agents in IBD by inducing anti-inflammatory cytokine pattern.