title: Proton pump inhibitor therapy in gastro-oesophageal reflux disease decreases the oesophageal immune response but does not reduce the formation of DNA adducts.
abstract: BACKGROUND
  Chronic oesophageal inflammation and related oxidative stress are important in the pathogenesis of erosive oesophagitis (EO) and its malignant progression.
  
  
  OBJECTIVE
  To study the effect of proton pump inhibitors (PPIs) on oesophageal cellular immune response and oxidative damage in EO patients.
  
  
  METHODS
  Forty gastro-oesophageal reflux disease (GERD) patients [non-erosive reflux disease (NERD): 15, EO: 25] were included, after 7 days off antisuppressive drugs. EO patients were randomized to 20-mg rabeprazole once daily for either 4 or 8 weeks with baseline and follow-up endoscopy with distal oesophageal biopsies. T lymphocytes, macrophages and mast cells were quantified by immunohistochemistry. DNA adducts were measured by analysis of 8-oxo-deoxyguanosine levels.
  
  
  RESULTS
  Erosive oesophagitis patients had more T lymphocytes and CD8(+) T lymphocytes in squamous epithelium than NERD patients (P = 0.001, P = 0.002, respectively). Levels of DNA adducts between both groups were, however, not different (P = 0.99). Four- and eight-week rabeprazole treatment in EO patients resulted in a significant decrease in number of T lymphocytes and CD8(+) T lymphocytes (all P < 0.05). PPIs did not, however, affect levels of DNA adducts.
  
  
  CONCLUSIONS
  Short-term PPI therapy in EO patients reduces the oesophageal cellular immune response, but does not change oxidative damage. PPI therapy may therefore not be effective in reducing the risk of oesophageal cancer in GERD patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Rotterdam, The Netherlands. p.dejonge@erasmusmc.nl
authors.forename: P J F
authors.initials: PJ
authors.lastname: De Jonge
authors.forename: P D
authors.initials: PD
authors.lastname: Siersema
authors.forename: S G J
authors.initials: SG
authors.lastname: Van Breda
authors.forename: K P M
authors.initials: KP
authors.lastname: Van Zoest
authors.forename: D J
authors.initials: DJ
authors.lastname: Bac
authors.forename: I
authors.initials: I
authors.lastname: Leeuwenburgh
authors.forename: R J Th
authors.initials: RJ
authors.lastname: Ouwendijk
authors.forename: H
authors.initials: H
authors.lastname: Van Dekken
authors.forename: J G
authors.initials: JG
authors.lastname: Kusters
authors.forename: E J
authors.initials: EJ
authors.lastname: Kuipers
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D001471:Barrett Esophagus / Q000276:immunology; D018736:DNA Adducts / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018736:DNA Adducts; D054328:Proton Pump Inhibitors; C067980:CD68 antigen, human; D000097382:CD68 Molecule