Dynamics of IFN-β responses during respiratory viral infection: insights for therapeutic strategies
Dynamics of IFN-β responses during respiratory viral infection: insights for therapeutic strategies
Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma and chronic obstructive pulmonary disease (COPD). IFN-β is a key component of the innate immune response to viral infection. To date, studies of inhaled IFN-β treatment have not demonstrated a significant effect on asthma exacerbations.Objectives: The dynamics of exogenous IFN-β activity were investigated to inform on future clinical indications for this potential antiviral therapy.Methods: Monocyte-derived macrophages (MDMs), alveolar macrophages, and primary bronchial epithelial cells (PBECs) were isolated from healthy control subjects and patients with COPD and infected with influenza virus either prior to or after IFN-β stimulation. Infection levels were measured by the percentage of nucleoprotein 1-positive cells using flow cytometry. Viral RNA shedding and IFN-stimulated gene expression were measured by quantitative PCR. Production of inflammatory cytokines was measured using MSD.Measurements and Main Results: Adding IFN-β to MDMs, alveolar macrophages, and PBECs prior to, but not after, infection reduced the percentage of nucleoprotein 1-positive cells by 85, 56, and 66%, respectively (P < 0.05). Inhibition of infection lasted for 24 hours after removal of IFN-β and was maintained albeit reduced up to 1 week in MDMs and 72 hours in PBECs; this was similar between healthy control subjects and patients with COPD. IFN-β did not induce inflammatory cytokine production by MDMs or PBECs but reduced influenza-induced IL-1β production by PBECs.Conclusions: In vitro modeling of IFN-β dynamics highlights the potential for intermittent prophylactic doses of exogenous IFN-β to modulate viral infection. This provides important insights to aid the future design of clinical trials of IFN-β in asthma and COPD.
Adult, Aged, Aged, 80 and over, Antiviral Agents/therapeutic use, Asthma/drug therapy, Female, Humans, Interferon-beta/therapeutic use, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive/drug therapy, Virus Diseases/drug therapy
83-94
Watson, Alastair
67936648-9486-403c-96b4-95aea4e833b4
Spalluto, C Mirella
6802ad50-bc38-404f-9a19-40916425183b
McCrae, Christopher
905349d4-6151-412b-b146-7f1481d8472b
Cellura, Doriana
e4cffc4c-0e12-40e7-ad13-e90e3fb55332
Burke, Hannah
a9bb9391-4704-4584-aeb7-e69fe0acbdb8
Cunoosamy, Danen
ea10b74c-a759-4a17-b71e-e6f20bdd6274
Freeman, Anna
3d83f907-e7ce-4649-a018-a7a31b19f934
Hicks, Alex
134bd066-ad67-4610-be2f-50a277caa4a9
Hühn, Michael
43e65a09-b883-4b5e-a21c-9fc3e044e44d
Ostridge, Kristoffer
b43a8cd5-e34d-4c5a-9e8f-ce404c94c53a
Staples, Karl J
e0e9d80f-0aed-435f-bd75-0c8818491fee
Vaarala, Outi
35ea8119-e804-402c-bb79-cfac625e71f5
Wilkinson, Tom
e6e24c51-d712-4202-8d87-e40f0e116b56
1 January 2020
Watson, Alastair
67936648-9486-403c-96b4-95aea4e833b4
Spalluto, C Mirella
6802ad50-bc38-404f-9a19-40916425183b
McCrae, Christopher
905349d4-6151-412b-b146-7f1481d8472b
Cellura, Doriana
e4cffc4c-0e12-40e7-ad13-e90e3fb55332
Burke, Hannah
a9bb9391-4704-4584-aeb7-e69fe0acbdb8
Cunoosamy, Danen
ea10b74c-a759-4a17-b71e-e6f20bdd6274
Freeman, Anna
3d83f907-e7ce-4649-a018-a7a31b19f934
Hicks, Alex
134bd066-ad67-4610-be2f-50a277caa4a9
Hühn, Michael
43e65a09-b883-4b5e-a21c-9fc3e044e44d
Ostridge, Kristoffer
b43a8cd5-e34d-4c5a-9e8f-ce404c94c53a
Staples, Karl J
e0e9d80f-0aed-435f-bd75-0c8818491fee
Vaarala, Outi
35ea8119-e804-402c-bb79-cfac625e71f5
Wilkinson, Tom
e6e24c51-d712-4202-8d87-e40f0e116b56
Watson, Alastair, Spalluto, C Mirella, McCrae, Christopher, Cellura, Doriana, Burke, Hannah, Cunoosamy, Danen, Freeman, Anna, Hicks, Alex, Hühn, Michael, Ostridge, Kristoffer, Staples, Karl J, Vaarala, Outi and Wilkinson, Tom
(2020)
Dynamics of IFN-β responses during respiratory viral infection: insights for therapeutic strategies.
American Journal of Respiratory and Critical Care Medicine, 201 (1), .
(doi:10.1164/rccm.201901-0214OC).
Abstract
Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma and chronic obstructive pulmonary disease (COPD). IFN-β is a key component of the innate immune response to viral infection. To date, studies of inhaled IFN-β treatment have not demonstrated a significant effect on asthma exacerbations.Objectives: The dynamics of exogenous IFN-β activity were investigated to inform on future clinical indications for this potential antiviral therapy.Methods: Monocyte-derived macrophages (MDMs), alveolar macrophages, and primary bronchial epithelial cells (PBECs) were isolated from healthy control subjects and patients with COPD and infected with influenza virus either prior to or after IFN-β stimulation. Infection levels were measured by the percentage of nucleoprotein 1-positive cells using flow cytometry. Viral RNA shedding and IFN-stimulated gene expression were measured by quantitative PCR. Production of inflammatory cytokines was measured using MSD.Measurements and Main Results: Adding IFN-β to MDMs, alveolar macrophages, and PBECs prior to, but not after, infection reduced the percentage of nucleoprotein 1-positive cells by 85, 56, and 66%, respectively (P < 0.05). Inhibition of infection lasted for 24 hours after removal of IFN-β and was maintained albeit reduced up to 1 week in MDMs and 72 hours in PBECs; this was similar between healthy control subjects and patients with COPD. IFN-β did not induce inflammatory cytokine production by MDMs or PBECs but reduced influenza-induced IL-1β production by PBECs.Conclusions: In vitro modeling of IFN-β dynamics highlights the potential for intermittent prophylactic doses of exogenous IFN-β to modulate viral infection. This provides important insights to aid the future design of clinical trials of IFN-β in asthma and COPD.
Text
Watson et al 2019 merged
- Accepted Manuscript
More information
Accepted/In Press date: 19 August 2019
e-pub ahead of print date: 28 August 2019
Published date: 1 January 2020
Additional Information:
Publisher Copyright:
Copyright © 2020 by the American Thoracic Society.
Keywords:
Adult, Aged, Aged, 80 and over, Antiviral Agents/therapeutic use, Asthma/drug therapy, Female, Humans, Interferon-beta/therapeutic use, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive/drug therapy, Virus Diseases/drug therapy
Identifiers
Local EPrints ID: 433602
URI: http://eprints.soton.ac.uk/id/eprint/433602
ISSN: 1073-449X
PURE UUID: 41a5d821-1989-48ea-b1a9-786ed5b6e3c7
Catalogue record
Date deposited: 28 Aug 2019 16:30
Last modified: 17 Mar 2024 02:54
Export record
Altmetrics
Contributors
Author:
Alastair Watson
Author:
C Mirella Spalluto
Author:
Christopher McCrae
Author:
Doriana Cellura
Author:
Hannah Burke
Author:
Danen Cunoosamy
Author:
Anna Freeman
Author:
Alex Hicks
Author:
Michael Hühn
Author:
Kristoffer Ostridge
Author:
Outi Vaarala
Author:
Tom Wilkinson
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics