title: Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis.
abstract: BACKGROUND
  Inflammation within the cystic fibrosis (CF) lung is mediated by inflammatory chemokines, such as IL-8. IL-8 is protected from proteolytic degradation in the airways by binding to glycosaminoglycans, while remaining active. Evidence that increased hypertonicity of airway secretions induced by hypertonic saline treatment alters levels of IL-8 is lacking.
  
  
  OBJECTIVE
  To investigate the antiinflammatory effect of hypertonic saline (HTS) treatment within the CF lung by focusing on IL-8.
  
  
  METHODS
  Degradation of IL-8 in CF lung secretions after treatment with glycosaminoglycan lyases and HTS was analyzed by Western blot analysis and ELISA. The ex vivo chemotactic activity of purified neutrophils in response to CF airway secretions was evaluated post nebulization of HTS (7% saline).
  
  
  RESULTS
  In vivo CF bronchoalveolar lavage fluid (BALF) IL-8 levels were significantly higher than the control group (P < 0.05). Digesting glycosaminoglycans in CF BALF displaced IL-8 from glycosaminoglycan matrices, rendering the chemokine susceptible to proteolytic cleavage. High sodium concentrations also liberate IL-8 in CF BALF in vitro, and in vivo in CF sputum from patients receiving aerosolized HTS, resulting in degradation of IL-8 and decreased neutrophil chemotactic efficiency.
  
  
  CONCLUSIONS
  Glycosaminoglycans possess the ability to influence the chemokine profile of the CF lung by binding and stabilizing IL-8, which promotes neutrophil chemotaxis and activation. Nebulized hypertonic saline treatment disrupts the interaction between glycosaminoglycans and IL-8, rendering IL-8 susceptible to proteolytic degradation with subsequent decrease in neutrophil chemotaxis, thereby facilitating resolution of inflammation.
authors.affiliation: Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland. emerreeves@rcsi.ie
authors.forename: Emer P
authors.initials: EP
authors.lastname: Reeves
authors.forename: Michael
authors.initials: M
authors.lastname: Williamson
authors.forename: Shane J
authors.initials: SJ
authors.lastname: O'Neill
authors.forename: Peter
authors.initials: P
authors.lastname: Greally
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006025:Glycosaminoglycans / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D016209:Interleukin-8 / Q000187:drug effects* / Q000276:immunology; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D013183:Sputum / Q000187:drug effects / Q000276:immunology*; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; D016209:Interleukin-8; D012462:Saline Solution, Hypertonic