[Cytokine expression in GERD].

The mechanism of esophageal mucosal injury has gradually been understood at the microbiological level. It is particularly important that pro-inflammatory factors, such as inflammatory cytokines, leukocytes and oxidative stress, have been demonstrated to be involved in the development of gastroesophageal reflux disease (GERD) including nonerosive reflux disease (NERD). Our present study reveals that expression of IL-8 mRNA, a potent neutrophil chemotactic and activating peptide, is correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration. In addition, it has been shown that bile acids and trypsin can promote IL-8 production from human esophageal epithelial cells via NFkappaB-and AP-1-dependent mechanism. Nociceptors such as acid-sensitive vanilloid receptors, protease-activated receptors and neuropeptides such as substance P have also been implicated in the pathogenesis of neurogenic inflammation in NERD patients with esophageal hypersensitivity. The development of new therapy with antiinflammatory and anti-oxidant effects is expected to assist in the treatment of intractable NERD/GERD and the prevention of carcinogenesis.