Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis

<p>Abstract</p> <p>Background</p> <p>Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively att...

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Main Authors: Brody Steven L, Cannon Carolyn L, Gunsten Sean P, Mikols Cassandra L, Beigelman Avraham, Walter Michael J
Format: Article
Language:English
Published: BMC 2010-06-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/11/1/90
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spelling doaj-a32b35b29bae4aa6859c6449bd4fbf372020-11-25T02:00:58ZengBMCRespiratory Research1465-99212010-06-011119010.1186/1465-9921-11-90Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitisBrody Steven LCannon Carolyn LGunsten Sean PMikols Cassandra LBeigelman AvrahamWalter Michael J<p>Abstract</p> <p>Background</p> <p>Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation.</p> <p>Methods</p> <p>Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV), and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL).</p> <p>Results</p> <p>Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8), azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21.</p> <p>Conclusions</p> <p>In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.</p> http://respiratory-research.com/content/11/1/90
collection DOAJ
language English
format Article
sources DOAJ
author Brody Steven L
Cannon Carolyn L
Gunsten Sean P
Mikols Cassandra L
Beigelman Avraham
Walter Michael J
spellingShingle Brody Steven L
Cannon Carolyn L
Gunsten Sean P
Mikols Cassandra L
Beigelman Avraham
Walter Michael J
Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
Respiratory Research
author_facet Brody Steven L
Cannon Carolyn L
Gunsten Sean P
Mikols Cassandra L
Beigelman Avraham
Walter Michael J
author_sort Brody Steven L
title Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
title_short Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
title_full Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
title_fullStr Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
title_full_unstemmed Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
title_sort azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis
publisher BMC
series Respiratory Research
issn 1465-9921
publishDate 2010-06-01
description <p>Abstract</p> <p>Background</p> <p>Viral bronchiolitis is the leading cause of hospitalization in young infants. It is associated with the development of childhood asthma and contributes to morbidity and mortality in the elderly. Currently no therapies effectively attenuate inflammation during the acute viral infection, or prevent the risk of post-viral asthma. We hypothesized that early treatment of a paramyxoviral bronchiolitis with azithromycin would attenuate acute and chronic airway inflammation.</p> <p>Methods</p> <p>Mice were inoculated with parainfluenza type 1, Sendai Virus (SeV), and treated daily with PBS or azithromycin for 7 days post-inoculation. On day 8 and 21 we assessed airway inflammation in lung tissue, and quantified immune cells and inflammatory mediators in bronchoalveolar lavage (BAL).</p> <p>Results</p> <p>Compared to treatment with PBS, azithromycin significantly attenuated post-viral weight loss. During the peak of acute inflammation (day 8), azithromycin decreased total leukocyte accumulation in the lung tissue and BAL, with the largest fold-reduction in BAL neutrophils. This decreased inflammation was independent of changes in viral load. Azithromycin significantly attenuated the concentration of BAL inflammatory mediators and enhanced resolution of chronic airway inflammation evident by decreased BAL inflammatory mediators on day 21.</p> <p>Conclusions</p> <p>In this mouse model of paramyxoviral bronchiolitis, azithromycin attenuated acute and chronic airway inflammation. These findings demonstrate anti-inflammatory effects of azithromycin that are not related to anti-viral activity. Our findings support the rationale for future prospective randomized clinical trials that will evaluate the effects of macrolides on acute viral bronchiolitis and their long-term consequences.</p>
url http://respiratory-research.com/content/11/1/90
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