Inflammatory Mediator Imbalances

In the healthy gut, the mucosal immune system ensures a balance between pro- and anti-inflammatory mediators. In inflammatory digestive disorders this immunological balance is severely impaired and is shifted towards the proinflammatory side. The prime factor behind inflammation induction is a protein complex called nuclear factor- kappa beta (NF-κβ) which acts as a switch to turn inflammation on and off in the body. This protein complex is sequestered in the cytoplasm of almost all cell types by an inhibitory protein kappa beta (Iκβ). NF-κβ plays a key role in regulating the immune response to infection and its incorrect regulation has been linked to cancer, inflammation and improper immune development. Once stimulated into action, NF-κβ sets off a cascade of proinflammatory cytokines such as tumor necrosis factor alpha (TNFα), interferon-gamma (IFN-γ) and interleukins-1, -6 & -12 (IL-1, IL-6, IL-12). Scientists describe NF-κβ as a “smoke sensor” that detects dangerous threats like infectious agents and free radicals.

The activation of NF-κβ can play a critical role in the development and perpetuation of many inflammatory disorders such as IBD and infectious colitis. Several groups have reported on increased intestinal NF-κβ activation in patients with inflammatory bowel disease as well as in animal models of inflammatory bowel disease. Consequently the NF-κβ pathway is an attractive target for therapeutic interventions. Many of the established immunosuppressive drugs used in inflammatory bowel disorders like corticosteroids, sulfasalazine and methotrexate are known to mediate their anti-inflammatory effects in part via inhibition of NF-κβ activity but are beset with side effects. Inclusion of all-natural bioactive ingredients with the potential to inhibit over-expression of NF-κβ and proinflammatory cytokines would be a welcome addition to a health care professional in helping to alleviate the inflammatory responses prominent in many digestive disorders.

            

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