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

Kak Ming Ling, Jessica Hillas, Melanie A. Lavender, Jeremy P. Wrobel, Michael Musk, Stephen M. Stick, Anthony Kicic

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and objective: Human rhinovirus (RV) is a common upper and lower respiratory pathogen in lung allograft recipients causing respiratory tract exacerbation and contributing towards allograft dysfunction and long-term lung decline. In this study, we tested the hypothesis that RV could infect both the small and large airways, resulting in significant inflammation. Methods: Matched large and small airway epithelial cells (AEC) were obtained from five lung allograft recipients. Primary cultures were established, and monolayers were infected with RV1b over time with varying viral titre. Cell viability, receptor expression, viral copy number, apoptotic induction and inflammatory cytokine production were also assessed at each region. Finally, the effect of azithromycin on viral replication, induction of apoptosis and inflammation was investigated. Results: RV infection caused significant cytotoxicity in both large AEC (LAEC) and small AEC (SAEC), and induced a similar apoptotic response in both regions. There was a significant increase in receptor expression in the LAEC only post viral infection. Viral replication was elevated in both LAEC and SAEC, but was not significantly different. Prophylactic treatment of azithromycin reduced viral replication and dampened the production of inflammatory cytokines post-infection. Conclusion: Our data illustrate that RV infection is capable of infecting upper and lower AEC, driving cell death and inflammation. Prophylactic treatment with azithromycin was found to mitigate some of the detrimental responses. Findings provide further support for the prophylactic prescription of azithromycin to minimize the impact of RV infection.

Original languageEnglish
JournalRespirology
DOIs
Publication statusE-pub ahead of print - 15 Apr 2019

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Rhinovirus
Azithromycin
Allografts
Inflammation
Lung
Epithelial Cells
Infection
Cytokines
Virus Diseases
Respiratory System
Prescriptions
Cell Survival
Cell Death
Apoptosis

Cite this

Ling, Kak Ming ; Hillas, Jessica ; Lavender, Melanie A. ; Wrobel, Jeremy P. ; Musk, Michael ; Stick, Stephen M. ; Kicic, Anthony. / Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients. In: Respirology. 2019.
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Azithromycin reduces airway inflammation induced by human rhinovirus in lung allograft recipients. / Ling, Kak Ming; Hillas, Jessica; Lavender, Melanie A.; Wrobel, Jeremy P.; Musk, Michael; Stick, Stephen M.; Kicic, Anthony.

In: Respirology, 15.04.2019.

Research output: Contribution to journalArticle

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AU - Ling, Kak Ming

AU - Hillas, Jessica

AU - Lavender, Melanie A.

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AU - Musk, Michael

AU - Stick, Stephen M.

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