title: The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing.
abstract: The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.
authors.affiliation: Howard Hughes Medical Institute, Departments of Internal Medicine, Pediatrics, and Physiology and Biophysics, and Nuclear Magnetic Resonance Facility, University of Iowa College of Medicine, Iowa City, IA 52242, USA. joseph-zabner@uiowa.edu
authors.forename: J
authors.initials: J
authors.lastname: Zabner
authors.forename: M P
authors.initials: MP
authors.lastname: Seiler
authors.forename: J L
authors.initials: JL
authors.lastname: Launspach
authors.forename: P H
authors.initials: PH
authors.lastname: Karp
authors.forename: W R
authors.initials: WR
authors.lastname: Kearney
authors.forename: D C
authors.initials: DC
authors.lastname: Look
authors.forename: J J
authors.initials: JJ
authors.lastname: Smith
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000328:Adult; D001419:Bacteria / Q000187:drug effects*; D001980:Bronchi / Q000737:chemistry / Q000187:drug effects* / Q000382:microbiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D015169:Colony Count, Microbial; D003550:Cystic Fibrosis / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000382:microbiology; D009994:Osmolar Concentration; D012492:Salts / Q000737:chemistry*; D014132:Trachea / Q000737:chemistry / Q000187:drug effects* / Q000382:microbiology; D014993:Xylitol / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D012492:Salts; D014993:Xylitol