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Nat Immunol. 2004 Apr;5(4):388-92. Epub 2004 Mar 21.

Defective lipoxin-mediated anti-inflammatory activity in the cystic fibrosis airway.

Author information

1
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

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.

PMID:
15034576
DOI:
10.1038/ni1056
[Indexed for MEDLINE]

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