ICS/LABA effects on antiviral innate immune response. An in vitro analysis

Inhaled corticosteroids (ICS) are the mainstay of asthma management. ICS/long-acting β2 agonists (LABA) combinations are widely used as maintenance treatment to prevent exacerbations in asthma and COPD. Viral infections are considered the main trigger of exacerbations in both obstructive lung diseases. However, there is concern on ICS suppression of the antiviral innate immune response. Here, we evaluated by qRT-PCR the modulatory effect of the ICS Budesonide (Bud), alone or in combination with the LABA Formoterol (Form), on interferon stimulated gene (ISG) expression and viral genome quantification in bronchial epithelial cells. BEAS2B cells were pre-treated for 1h with scalar concentrations of tested compounds before 1h rhinovirus 1B (HRV-1B) infection. Treatment was continued with tested compounds for 24h. Bud and to a lesser extent Form reduced in a dose-dependent manner mRNA expression of two antiviral ISGs, viperin and OAS. At a concentration of 1nM, Bud suppressed viperin and OAS gene expression of 92±6% and 82±9% respectively over control vehicle. At a concentration of 10nM, Form suppressed viperin and OAS of 60±36% and 45±42% respectively over control vehicle. The combination Bud0.1nM/Form10nM potentiated viperin and OAS gene suppression compared to the individual effects of Bud and Form at the same concentrations. Furthermore, we observed an increase of viral RNA after exposure to 10nM Bud (1.5-fold) but not Form. Thus, Bud and to a lesser extent Form impaired the early innate immune response in bronchial epithelial cells by suppression of antiviral ISG expression, an effect potentiated by the combination Bud/Form.