Abstract
Background Acute respiratory virus infections are common precipitants of asthma exacerbations, with most asthma exacerbations in adults and children due to human rhinovirus infection (RV). Asthma exacerbations are not well controlled by conventional steroid therapies and there is much research interest in finding improved therapies or combinations of existing therapies for asthma exacerbations. CHF6001 is a new highly potent and selective phosphodiesterase type 4 (PDE4) inhibitor designed for inhaled administration.
Methods By using in vitro human normal bronchial epithelial cells (BEAS-2B) we investigated the potential anti-inflammatory effects of CHF6001 on RV-induced cytokines upregulation. Cytokines mRNA levels were measured by real time PCR, while protein release by ELISA. CHF6001 was used in 7 point dose response curves (1000-0.001nM) as a 1h pre-treatment prior to infection in comparison with roflumilast which was used as above but as pre-treatment and post-treatment since pre-treatment only was not sufficient to elicit anti-inflammatory effects.
Results In BEAS-2B, both roflumilast and CHF6001 reduced RV1B induced IL-8, IL-29, IP-10 and RANTES/CCL5 mRNA and protein in a concentration dependent manner. Both CHF6001 and roflumilast had no effect on RV1B replication. Generally, CHF6001 was about 10-fold more potent (sub-nanomolar IC50s values) than roflumilast at reducing IL-8, IL-29, IP-10 and RANTES/CCL5 mRNA and protein release and showed greater suppression at both 1 and 0.1nM for each cytokine.
Conclusion The data support the idea that PDE4 inhibitors have anti-inflammatory activity against virus induced inflammatory mediators and that CHF6001 is more effective than roflumilast.
- © 2014 ERS
