title: Glucocorticosteroids enhance replication of respiratory viruses: effect of adjuvant interferon.
abstract: 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.
authors.affiliation: 1] Monash Lung and Sleep, Monash Medical Centre, Clayton, Victoria, 3168, Australia [2] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [3] Monash University, Clayton, Victoria, 3168, Australia.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Thomas
authors.affiliation: 1] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [2] Monash University, Clayton, Victoria, 3168, Australia.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Porritt
authors.affiliation: 1] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [2] Monash University, Clayton, Victoria, 3168, Australia.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hertzog
authors.affiliation: 1] Monash Lung and Sleep, Monash Medical Centre, Clayton, Victoria, 3168, Australia [2] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [3] Monash University, Clayton, Victoria, 3168, Australia.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Bardin
authors.affiliation: 1] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Clayton, Victoria, 3168, Australia [2] Monash University, Clayton, Victoria, 3168, Australia.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Tate
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D009980:Influenza A virus / Q000502:physiology*; D007372:Interferons / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000662:veterinary; D012229:Rhinovirus / Q000502:physiology*; D012720:Severity of Illness Index; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D016207:Cytokines; D005938:Glucocorticoids; D007372:Interferons