Effect of sucralfate on gastric mucosal inflammatory responses induced by Helicobacter pylori lipopolysaccharide.

BACKGROUND

Helicobacter pylori lipopolysaccharide is emerging as a primary factor in the bacterium virulence, and its involvement in causing gastric mucosal responses typical of gastritis has recently been shown. In this study we investigated the effect of the antiulcer agent sucralfate on the expression of regulatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4), and epithelial cell apoptosis during H. pylori lipopolysaccharide-induced acute gastritis.

METHODS

The experiments were conducted with rats pretreated intragastrically twice daily for 3 days with sucralfate at 100 mg/kg or the vehicle. The rats were then subjected to intragastric surface epithelial application of H. pylori lipopolysaccharide at 50 microg per animal and maintained on the sucralfate or vehicle regimen for an additional 4 days. The animals were killed 16 h after the last dose, and their gastric mucosal tissue used for histologic assessment, quantitation of TNF-alpha and IL-4 expression, and the assay of epithelial cell apoptosis.

RESULTS

In the absence of sucralfate, H. pylori lipopolysaccharide induced acute mucosal responses characterized by the inflammatory infiltration of the lamina propria, hyperemia, and epithelial hemorrhage. This was accompanied by an 11-fold increase in gastric epithelial cell apoptosis and a 9-fold enhancement of the mucosal expression of TNF-alpha, but the level of IL-4 fell by 15%. Intragastric administration of sucralfate produced a 62% reduction in the extent of mucosal damage caused by H. pylori lipopolysaccharide, a 51% decrease in the mucosal expression of TNF-alpha, and a 7-fold reduction in the extent of epithelial cell apoptosis, whereas the expression of IL-4 increased by 52%.

CONCLUSIONS

Gastric mucosal inflammatory responses to H. pylori lipopolysaccharide are characterized by a massive enhancement of the proinflammatory cytokine TNF-alpha and epithelial cell apoptosis and repression of IL-4. Our data also show that sucralfate is capable of inducing expression of the regulatory cytokine IL-4 and the suppression of apoptotic events triggered in gastric mucosa by the increase in TNF-alpha that is elicited by H. pylori lipopolysaccharide.