Azithromycin attenuates airway inflammation in a mouse model of viral bronchiolitis.
BACKGROUND
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.


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Beigelman
Avraham
A
Division of Allergy, Immunology & Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St, Louis, MO; USA. beigelman_a@kids.wustl.edu
Mikols
Cassandra L
CL
Gunsten
Sean P
SP
Cannon
Carolyn L
CL
Brody
Steven L
SL
Walter
Michael J
MJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D001990:Bronchiolitis, Viral / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D010222:Parainfluenza Virus 1, Human / Q000472:pathogenicity; D011014:Pneumonia / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010253:Respirovirus Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D029082:Sendai virus / Q000472:pathogenicity; D013997:Time Factors; D019562:Viral Load; D015431:Weight Loss / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D017963:Azithromycin