[The mechanisms of gastrointestinal mucosal injury and repair]

Peptic ulcer disease are usually accompanied by diffuse inflammation over the gastroduodenal mucosa in addition to severe local inflammation at the site of ulceration. It is well known that inflammatory cytokine are the main mediators of inflammation. Cytokines may also play a part in acute gastroduodenal mucosal lesions (AGML) caused by NSAID, H. pylori, and stress. Among cytokines most involved in AGML, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL) 1, IL-6, and IL-8 modulate chemotaxis, chemokinetics, and aggregation and release of lysosomal enzymes from neutrophils. Ulcer healing requires interaction of various cellular and connective tissue components. The stimulus for increased cell proliferation is most likely initiated by EGF and/or TGF-alpha which are mitogenic peptides for gastric epithelial cell at the initial stage in ulcer healing after ulcer induction. Transforming growth factor-beta (TGF-beta) also potentially involved in the ulcer healing process. During the chronic stage of ulceration, the growth of granulation tissue and generation of new microvessels by angiogenesis is stimulated by the fibroblast growth factors, platelet derived growth factor, TGF-beta, prostaglandins and/or IL-1 and TNF-alpha. The quality of mucosal restoration may be the most important factor in determining whether ulcers will recur. The proper restoration of the mucosal architecture requires balanced stimulation and interaction of both epithelial and connective tissue components, as well as, activation of growth factors which controls these components.