title: Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway.
abstract: In cystic fibrosis, dysregulated neutrophilic inflammation and chronic infection lead to progressive destruction of the airways. The underlying mechanisms have remained unclear. Lipoxins are anti-inflammatory lipid mediators that modulate neutrophilic inflammation. We report here that lipoxin concentrations in airway fluid were significantly suppressed in patients with cystic fibrosis compared to patients with other inflammatory lung conditions. We also show that administration of a metabolically stable lipoxin analog in a mouse model of the chronic airway inflammation and infection associated with cystic fibrosis suppressed neutrophilic inflammation, decreased pulmonary bacterial burden and attenuated disease severity. These findings suggest that there is a pathophysiologically important defect in lipoxin-mediated anti-inflammatory activity in the cystic fibrosis lung and that lipoxins have therapeutic potential in this lethal autosomal disease.
authors.affiliation: Division of Molecular Immunology, Cincinnati Children's Hospital Medical Center, and University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA. chris.karp@chmcc.org
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Karp
authors.forename: Leah M
authors.initials: LM
authors.lastname: Flick
authors.forename: Kiwon W
authors.initials: KW
authors.lastname: Park
authors.forename: Samir
authors.initials: S
authors.lastname: Softic
authors.forename: Todd M
authors.initials: TM
authors.lastname: Greer
authors.forename: Raquel
authors.initials: R
authors.lastname: Keledjian
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Jasim
authors.initials: J
authors.lastname: Uddin
authors.forename: William B
authors.initials: WB
authors.lastname: Guggino
authors.forename: Sowsan F
authors.initials: SF
authors.lastname: Atabani
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Belkaid
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Accurso
authors.forename: Marsha
authors.initials: M
authors.lastname: Wills-Karp
authors.forename: Nicos A
authors.initials: NA
authors.lastname: Petasis
mesh_terms: D003550:Cystic Fibrosis / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D044045:Lipoxins / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000378:metabolism
chemical_list: D044045:Lipoxins