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Conference/Presentation Title: Treating influenza A exacerbations: The case for pirfenidone over glucocorticoids.
Authors: Chitty J.;Montgomery B.;Bardin P. ;Bourke J.;Thomas B.
Institution: (Chitty, Bourke) Pharmacology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia
(Montgomery) Avalyn Pharma, Seattle, United States
(Bardin, Thomas) Monash Lung and Sleep, Monash Medical Centre and Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, Australia
Respiratory and Sleep Medicine
Hudson Institute - Centre for Innate Immunity and Infectious Diseases
Presentation/Conference Date: 3-May-2023
Copyright year: 2023
Publisher: John Wiley and Sons Inc
Publication information: Respirology. Conference: TSANZSRS 2023 Australia and New Zealand Society of Respiratory Science and The Thoracic Society of Australia and New Zealand (ANZSRS/TSANZ) Annual Scientific Meeting for Leaders in Lung Health and Respiratory Science. Christchurch New Zealand. 28(Supplement 2) (pp 28), 2023. Date of Publication: March 2023.
Journal: Respirology
Abstract: Introduction/Aim: Patients with respiratory diseases are more susceptible to viral infection and develop more severe symptoms, associated with immunosuppression by elevated transforming growth factor-beta (TGFbeta). Glucocorticosteroids (GCS) effectively reduce inflammation when inhaled prophylactically, or taken orally for exacerbations, but can also cause further immunosuppression. Oral pirfenidone (PFD), an anti-fibrotic used to treat patients with pulmonary fibrosis, has been shown to reduce TGFbeta-enhanced influenza A virus (IAV) infection in mice (Thomas et al., Respirology, 2021). The current aim was to determine if administration of inhaled PFD prior to infection, or with the addition of oral PFD post-infection, is as effective at reducing IAV-induced inflammation as GCS, without causing immunosuppression. Method(s): Mice were treated with i.n. vehicle (control), PFD (13.3 mg/kg) or GCS (1 mg/kg) daily, starting 2 days prior to infection with IAV (10 2 PFU, HKx31, n = 6-10). Separate mice were treated daily pre- and post-infection (i.n. then oral) with vehicle (i/o control), PFD (i/o PFD) or GCS (i/o GCS). Mice were culled 3 days post-infection to measure viral load, inflammation and immune responses in BALF and lung tissue. Result(s): Inhaled PFD, but not GCS, reduced viral load (p < 0.05). Both PFD and GCS reduced RANTES, while PFD, but not GCS, reduced IL-6, TNFalpha and KC. IAV-induced Inflammatory cells, notably macrophages and neutrophils, were further increased by GCS (p < 0.001) but not by PFD. Preliminary results suggest that i/o PFD reduced the severity of IAV infection, while i/o GCS increased severity. Conclusion : Treatment with either inhaled or i/o PFD afforded greater protection against TGFbeta-enhanced viral infection and inflammation than GCS. These positive findings support the repurposing of PFD beyond its current use in IPF to include other respiratory diseases, offering superior protection from worse disease outcomes associated with viral exacerbations.
Conference Name: TSANZSRS 2023 Australia and New Zealand Society of Respiratory Science and The Thoracic Society of Australia and New Zealand (ANZSRS/TSANZ) Annual Scientific Meeting for Leaders in Lung Health and Respiratory Science
Conference Start Date: 2023-03-25
Conference End Date: 2023-03-28
Conference Location: Christchurch, New Zealand
Type: Conference Abstract
Subjects: immune response
immunosuppressive treatment
inflammatory cell
influenza A
Influenza A virus
lung parenchyma
respiratory tract disease
interleukin 6
transforming growth factor beta
tumor necrosis factor
Type of Clinical Study or Trial: Observational study (cohort, case-control, cross sectional, or survey)
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