Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway.
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.
Karp
Christopher L
CL
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
Flick
Leah M
LM
Park
Kiwon W
KW
Softic
Samir
S
Greer
Todd M
TM
Keledjian
Raquel
R
Yang
Rong
R
Uddin
Jasim
J
Guggino
William B
WB
Atabani
Sowsan F
SF
Belkaid
Yasmine
Y
Xu
Yan
Y
Whitsett
Jeffrey A
JA
Accurso
Frank J
FJ
Wills-Karp
Marsha
M
Petasis
Nicos A
NA
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
D044045:Lipoxins