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Aliment Pharmacol Ther ; 40(8): 955-65, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25112708

RESUMO

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.


Assuntos
Eosinofilia/genética , Esofagite Eosinofílica/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Inibidores da Bomba de Prótons/farmacologia , Adolescente , Adulto , Idoso , Quimiocina CCL26 , Quimiocinas CC/genética , Regulação para Baixo , Eosinofilia/tratamento farmacológico , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/imunologia , Feminino , Humanos , Interleucina-13/genética , Interleucina-5/genética , Masculino , Pessoa de Meia-Idade , Inibidores da Bomba de Prótons/uso terapêutico , Células Th2/imunologia , Adulto Jovem
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