TY - JOUR T1 - Novel narrow spectrum kinase inhibitors inhibit rhinovirus replication via enhancement of interferon expression in nasal epithelial cells of atopic and non-atopic patients JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p3495 AU - Marco Contoli AU - Kazuhiro Ito AU - Donatella Poletti AU - Antonio Pastore AU - Alberto Papi Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p3495.abstract N2 - RATIONAL Rhinovirus infection is one of important causes of asthma exacerbation. Deficient innate immune response was reported in asthma accounting for increased susceptibility of asthmatic patients to respiratory viral infections. The aim of this study is to evaluate the effects of RV568 and RV1088, narrow spectrum kinase inhibitors (NSKIs), on HRV16 replication and interferon expression in nasal brushing epithelial cells (NBEC) from atopic (A) and non-atopic (NA) patients.Methods: NBECs were collected from 9 A- and 9 NA-rhinitis patients. Cells were treated with RV568, RV1088, fluticasone propionate (FP) or tiotropium bromide (TB), and infected with HRV16 (5MOI). After 1 hr absorption, cells were washed with PBS and then treated with compounds again. At 8hrs after infection, cells were collected to determine viral RNA and IFN-λ, IFN-β mRNAs by real time RT-PCR.Results: HRV16 viral load (copy number) was 9 fold higher in NBECs of A-patients than those of NA-patients (48.6×105 and 5.4×105, respectively, p=0.083). In addition, IFN-λ expression was significantly lower in A-patients than NA-patients (copy number, 801±122, 1363±174, p=0.02). IFN-β expression showed similar trends. Both RV568 (100nM) and RV1088 (10, 100nM) inhibited HRV16 replication, and significantly increased IFN-λ, -β expression, particularly in A-patients. FP (100nM) and TB (100nM) did not inhibit viral load or increase IFN expression.Conclusions: HRV16 infection is more severer in NBECs from A- compared to NA-patients due to deficient HRV16-induced IFN expression, that is restored by RV568 and RV1088. ER -