NEW YORK (Reuters Health) - Decreased levels of lipoxin may cause the pathogenic inflammatory responses observed in the lungs of patients with cystic fibrosis (CF), investigators report in the online edition of the April issue of Nature Immunology. In a murine model of CF, treatment with a lipoxin analog reduced the accumulation of neutrophils in the lung and decreased the bacterial burden after challenge.
Dr. Christopher L. Karp at the University of Cincinnati College of Medicine in Ohio and colleagues note that lipoxins are anti-inflammatory lipid mediators that regulate neutrophilic responses. In vivo experiments have previously shown that lipoxins promote the resolution of neutrophil-mediated inflammation.
In the current research, analysis of bronchial alveolar lavage fluids from patients with CF and patients with other inflammatory lung conditions showed lipoxin A4 (LXA4) concentrations were reduced in CF airways, as was the ratio of LXA4 to neutrophils. And when Dr. Karp’s team treated bronchial epithelial cells in vitro with a stable LXA4 analog and then stimulated them with P. aeruginosa, the agent inhibited IL-8 production.
The researchers then conducted in vivo experiments in mice with chronic airway inflammation resembling that of CF. They treated the mice with the lipoxin analog or with placebo, and after 24 hours challenged them with P. aeruginosa.
Five days later, active treatment was associated with decreased numbers of neutrophils in bronchoalveolar lavage fluid and in lung parenchyma. In airway fluid, the ratios of neutrophils to lymphocytes and to macrophages were significantly decreased, representing “a shift from ‘acute’ to ‘chronic’ inflammation.” There was also a decrease in pulmonary bacterial burden and significantly less weight loss.
These findings, the researchers conclude “indicate new approaches to both pathogenesis and therapy of this lethal genetic disease.”
Source: Nat Immunol 2004. [ Google search on this article ]
MeSH Headings:Neutrophils: Drugs, InvestigationalCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.