Azithromycin induces anti-viral effects in cultured bronchial epithelial cells from COPD patients

Abstract

Rhinovirus infection is a major cause of chronic obstructive pulmonary disease (COPD) exacerbations and may contribute to the development into severe stages of COPD. The macrolide antibiotic azithromycin may exert anti-viral actions and has been reported to reduce exacerbations in COPD. However, little is known about its anti-viral actions on bronchial epithelial cells at clinically relevant concentrations. Primary bronchial epithelial cells from COPD donors and healthy individuals were treated continuously with azithromycin starting 24 h before infection with rhinovirus RV16. Expression of interferons, RIG-I like helicases, pro-inflammatory cytokines and viral load were analysed. Azithromycin transiently increased expression of IFNβ and IFNλ1 and RIG-I like helicases in un-infected COPD cells. Further, azithromycin augmented RV16-induced expression of interferons and RIG-I like helicases in COPD cells but not in healthy epithelial cells. Azithromycin also decreased viral load. However, it only modestly altered RV16-induced pro-inflammatory cytokine expression. Adding budesonide did not reduce interferon-inducing effects of azithromycin. Possibly by inducing expression of RIG-I like helicases, azithromycin increased rhinovirus-induced expression of interferons in COPD but not in healthy bronchial epithelium. These effects would reduce bronchial viral load, supporting azithromycin’s emerging role in prevention of exacerbations of COPD.

Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients

“…production of sentinel inflammatory cytokines including IL-6, IL-8 and RANTES. Although the antiviral activity of azithromycin has been suggested to occur via its activation of the interferon-beta (IFN-β) pathway, 29,30 the fact that it had no effect on apoptosis in this study, a process typically induced by IFN-β, suggests an alternative mode of action, possibly via lung microbiome modification. 31 Our results appear consistent with that of others, who have demonstrated its antiviral and antiinflammatory nature [26][27][28] suggesting that prophylactic azithromycin may aid in protecting the lungs against viral infection and the resultant inflammatoryassociated damage.…”

“…Although recognized as a common cause of exacerbation and resultant damage in immunocompromised individuals, RV is not the only viral risk factor in allograft recipients. Work by others have identified respiratory syncytial virus (RSV) and influenza as prominent viral pathogens 24,29,30,32 in allograft recipients and hence further research is necessary in order to gain a better understanding of the effects of these respiratory viruses in the lower airways of lung allograft recipients.…”

Inflammation in cystic fibrosis: An update

“…Others report that azithromycin primes the host immune response to better resist viral infection . If true, then this mechanism may help to explain how chronic macrolide therapy reduces the risk of or improves recovery from acute pulmonary exacerbations for people with a variety of lung diseases, ranging from CF with or without P aeruginosa infection to COPD in older populations and bronchiolitis in young children . Most recently, azithromycin reduced the time to next exacerbation in young children with CF who developed newly identified P aeruginosa in respiratory cultures.…”

Promising approaches for the treatment and prevention of viral respiratory illnesses

“…Early in vivo evidence suggested that azithromycin has anti-inflammatory and antiviral effects through induction of interferon-stimulated gene mRNA expression and reduced viral replication and release in patients with asthma and chronic obstructive lung disease. 36,37 In a randomized clinical trial including wheezing preschool-aged children, early azithromycin administration significantly reduced the likelihood of a severe lower respiratory tract infection. 38 Novel macrolides (Mycobacterium avium complex 5) with anti-inflammatory, antibacterial, and, more importantly, interferon-augmenting activity in airway epithelium have been identified.…”