TY - JOUR T1 - Azithromycin fails to restore apoptosis in cystic fibrosis airway epithelium post viral infection JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 1449 AU - Erika Sutanto AU - Clara Foo AU - Anthony Kicic AU - Stephen Stick AU - ARESTCF Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/1449.abstract N2 - Rationale: Airway epithelium is primary target for respiratory viruses, especially human rhinovirus (HRV). Apoptosis as early host defense mechanisms is induced in response to viral infection. We have previously observed damped apoptotic & increased viral replication in cystic fibrosis (CF) airway epithelium compared to healthy controls. Azithromycin induces innate immune responses in non-CF epithelium. We hypothesize that addition of azithromycin to HRV-infected CF cells may restore/elevate their current apoptotic response to viral insult.Methods: Airway epithelial cells (AEC) from healthy children (HNA) & those with CF were infected with HRV1b at various multiplicities of infection (MOI: 3-25). AECs were either pre-treated for 24hr or co-treated with azithromycin (1-10μM). Viral replication was determined using qPCR, apoptosis assessed using ssDNA apoptosis kit & IL-8 measured via ELISA.Results: HRV1b replication was 10-fold greater in CF compared to HNA despite the expression of HRV1b-specific receptor remaining the same between the two cohorts. Furthermore, CF exhibited a dampened apoptotic (∼2 fold) compared to the healthy counterparts. Pre- or co-treatment of CF AEC with azithromycin had little effect in restoring apoptosis to levels seen in healthy cells. Azithromycin also did not reduce the level of IL-8 in CF in response to HRV infection.Conclusion: Although CF are more susceptible to HRV1b infection, the dampened apoptotic response seen in CF epithelium after HRV infection cannot be restored with pre or co-treatment with azithromycin. The increased production of IL-8 observed post viral infection was not ameliorated following macrolide treatment.Funding: NHMRC, ARC, ACFRT. ER -