Increased rhinovirus replication following corticosteroid and air pollution exposures

Abstract

Respiratory tract infections have been linked to air pollution exposure, and both are known exogenous risk factors of asthma exacerbations. The current frontline therapy used to minimize exacerbations are inhaled corticosteroids (ICS), but these medications increase the risk of respiratory tract infections in patients due to immunosuppressive side-effects. Virally-triggered exacerbations are most commonly associated with rhinovirus, and the ICS fluticasone propionate (FP) has been demonstrated to increase rhinovirus viral load by 2.5-fold in infected epithelial cells. We hypothesized that air pollution exposure combined with ICS would magnify effects on host-defence antiviral responses and viral replication. Using rhinovirus (RV16), we infected human bronchial epithelial (BEAS-2B) cells that were pre-treated with FP (250 nM) and exposed to diesel exhaust particles (DEP) SRM2975 (50 μg/cm²). We show that DEP exposure significantly increased RV16 viral RNA by 12-fold over untreated cells 24 h post-infection, while FP alone induced a 2-fold rise. However, when combined, FP and DEP induced a significant supra-additive 17-fold increase in RV16 RNA. In addition, we demonstrate that DEP induces the expression of the RV16 entry receptor ICAM-1 through the canonical NF-κB pathway and that suppression of this pathway results in attenuation of RV16 viral expression. Our findings suggest a mechanism through which combined epithelial exposure to DEP and ICS increases RV16 infectivity through the suppression of innate antiviral immune responses and induction of the RV16 entry receptor ICAM-1. These findings suggest a need for caution during periods of high air pollution by those managing chronic lung diseases with corticosteroids.

Keywords: Host-defence response; Inhaled corticosteroid; Rhinovirus; Traffic-related air pollution.