Potassium-Competitive Acid Blocker Increases Ileal Permeability and Exacerbates Ileal Inflammation under Stress Conditions in a Mouse Model of Eosinophilic Enteritis.

INTRODUCTION

Potassium-competitive acid blockers (P-CABs) have been empirically administered to treat non-esophageal eosinophilic gastrointestinal diseases, although their efficacy remains unproven. Our previous findings demonstrated that psychological stress impairs the intestinal barrier and exacerbates eosinophilic enteritis (EoN) in a mouse model. Moreover, we demonstrated that P-CAB increased intestinal permeability under psychological stress. The aim of this study was to clarify the hypothesis that P-CAB exacerbate EoN by increasing intestinal permeability under stressful conditions.

METHODS

An EoN model was established in BALB/c mice using ovalbumin (OVA) sensitization and challenge. Mice were subjected to water avoidance stress (WAS) or sham stress (SS) and were administered P-CAB or saline as a vehicle. The ileum was collected for the analysis of ileal microscopic inflammation, mRNA and protein expression levels of T helper type 2 (Th2) cytokines, and ex vivo ileal permeability using a Ussing chamber.

RESULTS

Compared with the WAS + vehicle group, WAS + P-CAB significantly exacerbated the incidence of diarrhea, villus/crypt ratio, eosinophil and mast cell counts, mRNA and protein levels of Th2 cytokines, OVA-specific immunoglobulin E protein levels, and ileal permeability. Larazotide acetate, a zonulin inhibitor, significantly improved ileal inflammation and decreased ileal permeability in the WAS + P-CAB-treated EoN mice.

CONCLUSIONS

P-CAB increased ileal permeability and exacerbated EoN under stressful conditions. Furthermore, a zonulin inhibitor demonstrated therapeutic effects in EoN with P-CAB under stressful conditions.