Belinda J Thomas 1, Rebecca A Porritt 2, Paul J Hertzog 2, Philip G Bardin 1, Michelle D Tate 2

PMID: 25417801 PMCID: PMC5384105 DOI: 10.1038/srep07176


Glucocorticosteroids (GCS) are used on a daily basis to reduce airway inflammation in asthma and chronic obstructive pulmonary disease (COPD). This treatment is usually escalated during acute disease exacerbations, events often associated with virus infections. We examined the impact of GCS on anti-viral defences and virus replication and assessed supplementary interferon (IFN) treatment. Here, we report that treatment of primary human airway cells in vitro with GCS prior to rhinovirus (RV) or influenza A virus (IAV) infection significantly reduces the expression of innate anti-viral genes and increases viral replication. Mice given intranasal treatment with GCS prior to IAV infection developed more severe disease associated with amplified virus replication and elevated inflammation in the airways. Adjuvant IFN treatment markedly reduced GCS-amplified infections in human airway cells and in mouse lung. This study demonstrates that GCS cause an extrinsic compromise in anti-viral defences, enhancing respiratory virus infections and provides a rationale for adjuvant IFN treatment.

Keywords: Adjuvants, Immunologic / pharmacology
Antiviral Agents / pharmacology
Cells, Cultured
Cytokines / metabolism
Epithelial Cells / cytology
Epithelial Cells / virology
Glucocorticoids / pharmacology*
Immunity, Innate / drug effects
Influenza A virus / physiology*
Interferons / pharmacology*
Lung / metabolism
Lung / pathology
Lung / virology
Mice, Inbred C57BL
Orthomyxoviridae Infections / pathology
Orthomyxoviridae Infections / veterinary
Rhinovirus / physiology*
Severity of Illness Index
Virus Replication / drug effects*