Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis

Abstract

BackgroundViral 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.MethodsMice 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).ResultsCompared 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.ConclusionsIn 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.

A randomised, double-blind, placebo-controlled study to evaluate the efficacy of oral azithromycin as a supplement to standard care for adult patients with acute exacerbations of asthma (the AZALEA trial)

“…27 Azithromycin has also been shown to reduce illness severity in a mouse model of viral bronchiolitis. 28 Thus, azithromycin has the potential to have direct antiviral activity by augmenting the production of those interferons that we have already shown to be deficient in asthma exacerbations, 20,26 and this activity may make it a better treatment option than telithromycin, which does not appear to have this property. 27 A further mechanistic aim of our study, therefore, was to investigate the frequencies of standard bacterial, atypical bacterial and viral infections in these exacerbations to determine the relative importance of each of these infections, and of possible coinfections with one or more agents, in the aetiology of acute exacerbations of asthma in adult subjects.…”

Efeito anti-inflamatório dos macrolídeos em doenças pulmonares da infância

“…Clarithromycin and azithromycin have been shown to be efficient in reducing airway inflammation, the former having been associated with decreased airway edema and decreased TNF-α, IL-1, and IL-10 concentrations in nasal aspirates. (8,44,45) One group of authors demonstrated that azithromycin decreased IL-5 production in lymphocytes of children with atopic asthma, without affecting IFN-γ production, thereby showing that azithromycin has a beneficial effect on the pathogenesis of asthma. (40) Even with all of these theoretical justifications based on experimental or mechanistic studies, (46) the positive effects of macrolides has not been consistent in the published clinical trials in Anti-inflammatory effects of macrolides in childhood lung diseases J Bras Pneumol.…”

“…(7) Other reported effects include reduced goblet cell secretion, reduced bronchoconstriction induced by a decreased release of endothelin-1, and inhibition of the cholinergic response in the airway smooth muscle. (2,8) A summary of the anti-inflammatory mechanisms is provided in Chart 1.…”

“…(5) Among the most important effects of macrolides are the inhibition of pro-inflammatory cytokine synthesis and secretion and the increase in antiinflammatory cytokine secretion, as well as effects on neutrophil activity via inhibition of neutrophil migration to sites of inflammation. (6,7) Macrolides can also inhibit leukocyte degranulation, reduce eosinophilic inflammation, activate macrophage phagocytic activity, (7) and increase mucociliary transport, reducing mucus production in vivo (8,9) and in vitro. (6) In addition, these drugs can have an effect on adaptive immunity via regulation of T-cells and of antigen presentation.…”

Effect of single-dose extended-release oral azithromycin on anticoagulation status in warfarinized patients

“…Azithromycin is an azalide, a subclass of macrolide antibiotics 9) . Some case reports have suggested that macrolides have the potential to enhance the anticoagulation effect of warfarin [1][2][3] .…”