title: Nebulized thiocyanate improves lung infection outcomes in mice.
abstract: OBJECTIVE
  Nebulized saline solutions are used in the treatment of multiple pulmonary diseases including cystic fibrosis (CF), asthma and chronic obstructive pulmonary disease (COPD). The benefits of these therapies include improved lung function, phlegm clearance and fewer lung infections. The thiocyanate anion (SCN) is a normal component of the airway epithelial lining fluid (ELF) secreted by pulmonary epithelia with antioxidant and host defence functions. We sought to test if SCN could be nebulized to combat lung infection by bolstering innate immune defence and antioxidant capacity.
  
  
  METHODS
  We established an effective antioxidant concentration of SCN in vitro using a bronchiolar epithelial cell line. We then developed a nebulization method of SCN in mice that increased ELF SCN above this concentration up to 12 h and used this method in a prolonged Pseudomonas aeruginosa infection model to test if increasing SCN improved host defence and infection outcomes.
  
  
  RESULTS
  SCN protected against cytotoxicity in vitro from acute and sustained exposure to inflammation-associated oxidative stress. Nebulized SCN effectively reduced bacterial load, infection-mediated morbidity and airway inflammation in mice infected with P. aeruginosa. SCN also sustained adaptive increases in reduced GSH in infected mice.
  
  
  CONCLUSIONS
  SCN is a dually protective molecule able to both enhance host defence and decrease tissue injury and inflammation as an antioxidant. Nebulized SCN could be developed to combat lung infections and inflammatory lung disease.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Chandler
authors.forename: E
authors.initials: E
authors.lastname: Min
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: D P
authors.initials: DP
authors.lastname: Nichols
authors.forename: B J
authors.initials: BJ
authors.lastname: Day
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D058491:Bacterial Load; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D002452:Cell Count; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide; D006997:Hypochlorous Acid; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology; D008297:Male; D008810:Mice, Inbred C57BL; D009330:Nebulizers and Vaporizers; D016877:Oxidants; D009195:Peroxidase; D010544:Peroxidases / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa; D011710:Pyocyanine / Q000378:metabolism; D013861:Thiocyanates / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000975:Antioxidants; D016207:Cytokines; D016877:Oxidants; D013861:Thiocyanates; D006997:Hypochlorous Acid; D011710:Pyocyanine; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase; C031760:thiocyanate