title: The effect of gastric juice on interleukin-8 production by cystic fibrosis primary bronchial epithelial cells.
abstract: CF patients are often treated with proton pump inhibitors (PPIs) to reduce acidic gastro-esophageal reflux (GER) and bronchial aspiration of duodeno-gastric contents is common in CF. We have previously demonstrated that gastric juice (GJ) from patients "on" PPI can induce interleukin-8 (IL-8) production by bronchial epithelial cells in culture. We hypothesized that such effect would be more pronounced in CF patients known to have high inflammatory susceptibility. We aimed to evaluate the effect of GJ on IL-8 production by primary bronchial epithelial cells (PBEC), derived from a CF patient and a healthy subject.
  
  
  METHODS
  PBEC obtained from one donor (normal PBEC) and one receptor (CF-PBEC) for lung transplantation were stimulated with GJ from patients "off" and "on" PPI. IL-8 levels were measured in the supernatant.
  
  
  RESULTS
  GJ from patients "on" PPI provoked a significant higher IL-8 production compared to GJ from patients "off" PPI, both in normal PBEC [462 (200-1468) vs. 11 (4-28) pg/ml, p=0.0001] as in CF-PBEC [1468 (841-2449) vs. 85 (26-131) pg/ml, p<0.0001]. Exposure of the cells to GJ "off" PPI and "on" PPI provoked significantly higher IL-8 production in the CF-PBEC compared to the normal PBEC ["off" PPI 85 (26-131) vs. 11 (4-28) pg/ml, p=0.01; "on" PPI 1468 (841-2449) vs. 462 (200-1468) pg/ml, p=0.01]. Filtration (0.20 μm) of the GJ "on" PPI, to eliminate large particles and bacterial sub-products, resulted in a significant decrease of IL-8 production.
  
  
  CONCLUSIONS
  Patients with CF, treated with PPIs, have GJ with high pH and high endotoxin levels. These patients often have GER and bronchial aspiration. The aspirated material (GJ "on" PPI) has a significantly enhanced inflammatory effect on CF bronchial epithelial cells in culture. As chronic PPI treatment in CF may result in a paradoxically increased inflammatory effect in the airways, alternative anti-reflux therapies should be considered in CF.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Herestraat 49, bus 701, 3000 Leuven, Belgium. Electronic address: ans.pauwels@med.kuleuven.be.
authors.forename: Ans
authors.initials: A
authors.lastname: Pauwels
authors.forename: Stijn
authors.initials: S
authors.lastname: Verleden
authors.forename: Ricard
authors.initials: R
authors.lastname: Farre
authors.forename: Bart M
authors.initials: BM
authors.lastname: Vanaudenaerde
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Raemdonck
authors.forename: Geert
authors.initials: G
authors.lastname: Verleden
authors.forename: Daniel
authors.initials: D
authors.lastname: Sifrim
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Dupont
mesh_terms: D001980:Bronchi / Q000166:cytology*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000503:physiopathology*; D004847:Epithelial Cells / Q000378:metabolism*; D005750:Gastric Juice / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use
chemical_list: D016209:Interleukin-8; D054328:Proton Pump Inhibitors
keywords: Gastric juice; Gastro-esophageal reflux; Human bronchial epithelial cells; Interleukin-8; Proton pump inhibitors