Inflammation in IBD
Inflammation in IBD and function of TNFα
The pathogenesis of inflammatory bowel disease begins with injury to the gastrointestinal mucosa, diminishing the integrity of this barrier. Then, either chronic or repetitive assault from gastrointestinal bacteria or antigens leads to stimulation of inflammatory processes. Activation of antigen-presenting cells promotes the differentiation of helper T cells, which enter a self-sustaining cycle with macrophages when combined with key cytokines (IFN = interferon). The activated macrophage
then secretes TNFα.
TNFα plays a major role in the inflammation process. It acts at 4 levels: Activated macrophages secrete inflammatory cytokines, which increase the inflammation. Activated entothelial cells secrete adhesion molecules, which allow the migration of inflammatory cells into the tissue. Activated fibroblasts secrete metalloproteinases and collagen, which results in tissue remodelling. Increased permeability results in impaired barrier function.
In the self-sustaining inflammatory cycle, macrophages produce all of the following EXCEPT:
Extra info: To a great extent, the cyclic nature of the inflammatory process is due to macrophageal generation of IL-12 and IL-18, which stimulates macrophage reponse.