Mucosal barrier injury of the gastrointestinal tract.

Mucosal barrier injury occurs in 4 phases. The first phase is the inflammatory/vascular phase and is characterised by the induction of proinflammatory cytokines interleukin (IL)-1, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma by cytotoxic drugs and irradation while the epithelial cells are still intact. The second phase is the epithelial phase when cells cease dividing and die. This coincides with neutropenia. The third phase is when necrosis and ulceration occur and is when the resident microbial flora and their products, e.g., endotoxin, translocate into the bloodstream. Moreover, impaired local defenses and lower levels of secretory IgA may allow local infection to develop. The final phase is when healing takes place. It involves the action of naturally occurring substances including trefoils, epithelial growth factors (EGFs), and transforming growth factors (TGFs). The events that take place in the gut are almost certainly more complicated than those occurring in the oral cavity since the gastrointestinal tract is intrinsically more complex in terms of its function. It possesses the specialized gastrointestinal-associated lymphoid tissue (GALT) system, and its resident microflora are more numerous and varied.

Blijlevens et al.¹⁷