Prostaglandins and Mucosal Defensive Mechanisms

The first line of mucosa! defence includes the juxtamucosal unstirred layer/pH gradient and the apical surface of the luminal epithelial cells. Many damaging agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), can overwhelm these defences and destroy extensive regions of the luminal epithelium. This damage is readily tolerated in the normal mucosa. Furthermore, a combination of increased mucosal bloodflow, epithelial migration, mucus release, and efflux of bicarbonate- rich fluid usually allows rapid recovery of mucosa I integrity. In the presence of vascular damage and congestion, however, luminal acid can kill mucosal cells and destroy the substrate necessary for repair (by epithelial migration). Damage of this type results in the production of hemorrhagic erosions, which may then develop into chronic ulceroinflammatory disease if healing is prevented by excess luminal acid or by impaired mucosal immune response. Endogenous and exogenous prostaglandins could affect all aspects of the mucosal defensive responses, from the juxtamucosal unstirred layer/pH gradient (via effects on secretion of bicarbonate, acid and mucus, as well as stimulation of fluid efflux) to the function of the mucosal immune system. Protection against the acute damage produced by topically administered NSAIDs or concentrated ethanol can result from either administration of prostaglandins or topical application of'mild irritants'. This is referred to as 'adaptive cytoprotection'. Parenterally administered NSAIDs can also produce mucosa! erosions. Protection against this type of damage may depend on the effects of prostaglandins on neural and contractile elements in the mucosa. Studies on animal models also suggest that by preventing acute hemorrhagic erosions, prostaglandins may prevent the development of chronic ulcer in susceptible individuals.