Diminished luminal release of esophageal epidermal growth factor in patients with reflux esophagitis

It has recently been demonstrated that human esophageal mucosa, containing numerous submucosal mucous glands, has the ability to elaborate significant amounts of esophageal epidermal growth factor (eEGF). Because of its role in the maintenance of the integrity of the esophageal mucosa, we elected to study the rate of secretion of eEGF in patients with reflux esophagitis (RE), compared with controls, using our newly developed esophageal perfusion model.

Fourteen healthy asymptomatic volunteers and 14 patients with endoscopically confirmed esophagitis underwent esophageal perfusion with saline, HCl (0.01 M, pH 2.1) HCl/pepsin (0.5 mg/ml of HCl), and ending NaCl solution during four consecutive 8-min perfusion periods. All perfusates were assayed for EGF by RIA (Amersham). Results are expressed as mean +/- SEM. Student's t test was used for statistical analysis.

The basal rate of luminal EGF release in patients with RE was 3.78 +/- 0.29 ng/min. This value significantly declined (2.27 +/- 0.27 ng/min; p < 0.001) during mucosal exposure to HCl but was significantly enhanced when the HCl perfusing solution was supplemented with pepsin (4.20 +/- 0.29; p < 0.001 vs. HCl). Introduction of saline during the last perfusion period maintained a rate of luminal EGF release similar to that observed during the initial esophageal perfusion with saline. Luminal release of EGF in patients with RE was significantly lower, compared with corresponding values recorded in controls during perfusion with saline (3.78 +/- 0.29 vs. 14.1 +/- 1.25 ng/min; p < 0.00001), with HCl (2.27 +/- 0.27 vs. 5.95 ng/min; p < 0.0001), with HCl/pepsin solution (4.2 +/- 0.29 vs. 11.7 +/- 1.88 ng/min; p < 0.0001), and during the final perfusion period with saline (3.73 +/- 0.25 vs. 15.1 +/- 1.1 ng/min; p < 0.00001). Therefore, the rate of luminal EGF release in controls was 4-fold, 3-fold, 3-fold, and 4-fold higher than that of patients with RE during perfusion with initial saline, HCl, HCl/pepsin and final saline, respectively.

1) Decreased esophageal EGF in patients with RE may facilitate the development or delay the healing of mucosal injury. 2) Depletion of EGF from the mucus layer covering the epithelium under the impact of refluxed luminal acid/pepsin may be considered as one of the potential underlying mechanisms leading to damage of the esophageal mucosa during gastroesophageal reflux episodes.