• Eur. J. Pharmacol. · Feb 2021

    Comparative Study

    Glucocorticoids impair type I IFN signalling and enhance rhinovirus replication.

    • Andrea Marcellini, Dawid Swieboda, Anabel Guedán, Stuart N Farrow, Paolo Casolari, Marco Contoli, Sebastian L Johnston, Alberto Papi, and Roberto Solari.
    • Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy. Electronic address: mrcndr@unife.it.
    • Eur. J. Pharmacol. 2021 Feb 15; 893: 173839.

    AbstractInhaled corticosteroids (ICS) are recommended treatments for all degrees of asthma severity and in combination with bronchodilators are indicated for COPD patients with a history of frequent exacerbations. However, the long-term side effects of glucocorticoids (GCs) may include increased risk of respiratory infections, including viral triggered exacerbations. Rhinovirus (RV) infection is the main trigger of asthma and COPD exacerbations. Thus, we sought to explore the influence of GCs on viral replication. We demonstrate the ICS fluticasone propionate (FP) and two selective non-steroidal (GRT7) and steroidal (GRT10) glucocorticoid receptor (GR) agonists significantly suppress pro-inflammatory (IL-6 and IL-8) and antiviral (IFN-λ1) cytokine production and the expression of the interferon-stimulated genes (ISGs) OAS and viperin in RV-infected bronchial epithelial cells, with a consequent increase of viral replication. We also show that FP, GRT7 and GRT10 inhibit STAT1 Y701 and/or STAT2 Y690 phosphorylation and ISG mRNA induction following cell stimulation with recombinant IFN-β. In addition, we investigated the effects of the ICS budesonide (BD) and the long-acting β2 agonist (LABA) formoterol, alone or as an ICS/LABA combination, on RV-induced ISG expression and viral replication. Combination of BD/formoterol increases the suppression of OAS and viperin mRNA observed with both BD and formoterol alone, but an increase in viral RNA was only observed with BD treatment and not with formoterol. Overall, we provide evidence of an impairment of the innate antiviral immune response by GC therapy and the potential for GCs to enhance viral replication. These findings could have important clinical implications.Copyright © 2020 Elsevier B.V. All rights reserved.

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