Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal...

Area of Science:

• Gastroenterology
• Immunology
• Pediatrics

Background:

• Proton pump inhibitors (PPIs) reduce gastric acid secretion and exhibit anti-inflammatory effects.
• PPIs suppress Th2-cytokine-stimulated eotaxin-3 expression by esophageal epithelial cells via acid-independent mechanisms.
• Esophageal eosinophilia is linked to elevated eotaxin-3 levels.

Purpose of the Study:

• To investigate the acid-inhibitory and acid-independent effects of PPIs on esophageal eosinophilia.
• To examine eotaxin-3 expression in the proximal and distal esophagus of children with eosinophilic esophagitis before and after PPI therapy.
• To assess the in vitro effects of acid and bile salts on IL-13-stimulated eotaxin-3 expression.

Main Methods:

• Retrospective analysis of 10 children with esophageal eosinophilia who underwent PPI treatment.
• Correlation of epithelial eotaxin-3 immunostaining with eosinophil counts in esophageal biopsies.
• In vitro study of eotaxin-3 secretion from esophageal squamous cells stimulated with IL-13 and exposed to varying pH and bile salt conditions, with or without omeprazole.

Main Results:

• A strong correlation was observed between peak eosinophil numbers and peak eotaxin-3-positive epithelial cells.
• PPI treatment significantly decreased eotaxin-3 expression in the proximal esophagus but not the distal esophagus.
• In vitro, acid-bile salt medium suppressed IL-13-induced eotaxin-3 secretion; omeprazole further suppressed secretion, though less effectively in acidic conditions.

Conclusions:

• PPIs reduce eotaxin-3 expression in the proximal esophagus of children with eosinophilic esophagitis.
• Acid and bile salts profoundly decrease Th2 cytokine-stimulated eotaxin-3 secretion in esophageal cells.
• The findings suggest that acid reflux in the distal esophagus may influence PPI efficacy by potentially masking acid-independent anti-inflammatory effects.