Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression

Aliment Pharmacol Ther. 2014 Oct;40(8):955-65. doi: 10.1111/apt.12914. Epub 2014 Aug 11.

Abstract

Background: The molecular basis and effects of proton pump inhibitor (PPI) therapy on PPI-responsive oesophageal eosinophilia (PPI-REE) and eosinophilic oesophagitis (EoE) remain unknown.

Aim: To compare symptom-histological and cytokine gene expression in PPI-REE and EoE patients, at baseline and after specific treatment.

Methods: In consecutive adult patients with an EoE phenotype (dysphagia/food impaction, typical endoscopic findings and > 15 eos/HPF), gene expression of eotaxin-3, IL-13, and IL-5 were determined in distal and proximal oesophagus, at baseline and after omeprazole 40 mg b.d. for 8 weeks. PPI-REE was defined by clinicohistological response. PPI nonresponders (EoE) were offered treatment with topical steroids.

Results: Fifty three patients were re-evaluated on PPI therapy. 23 patients (43%) had PPI-REE and 30 patients (57%) had EoE. At baseline, eotaxin-3/IL-13/IL-5 gene expression was indistinguishable between EoE and PPI-REE, excepting increased IL-5 expression in proximal oesophagus (12.54 vs. 57, P = 0.029). PPI therapy significantly decreased eotaxin-3/IL-13 in PPI-REE, at both oesophageal sites (P ≤ 0.008), and IL-5 in distal (P = 0.016), but not in proximal oesophagus. Patients with steroid-responsive EoE also showed a significant decrease in eotaxin-3/IL-5 expression at both oesophageal sites. In EoE patients, initial PPI trial significantly decreased distal oesophageal eosinophilia (63.78 to 41.79 eos/HPF, P = 0.025) and led to symptom remission in 16%, but did not influence Th2 markers.

Conclusions: Baseline cytokine gene expression in PPI-REE was nearly indistinguishable from EoE. PPI therapy significantly downregulated oesophageal eotaxin-3/Th2-cytokine gene expression in PPI-REE, similarly to that seen in steroid-responsive EoE. A subset of EoE patients showed clinicohistological improvement on PPI therapy.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Chemokine CCL26
  • Chemokines, CC / genetics
  • Down-Regulation
  • Eosinophilia / drug therapy
  • Eosinophilia / genetics*
  • Eosinophilic Esophagitis / drug therapy
  • Eosinophilic Esophagitis / genetics*
  • Eosinophilic Esophagitis / immunology
  • Female
  • Gene Expression Regulation / drug effects*
  • Humans
  • Interleukin-13 / genetics
  • Interleukin-5 / genetics
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / pharmacology*
  • Proton Pump Inhibitors / therapeutic use
  • Th2 Cells / immunology
  • Young Adult

Substances

  • CCL26 protein, human
  • Chemokine CCL26
  • Chemokines, CC
  • IL13 protein, human
  • IL5 protein, human
  • Interleukin-13
  • Interleukin-5
  • Proton Pump Inhibitors