Abstract
Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma and COPD. IFN-β is a key component of the innate immune response to viral infection. However, in the recent INEXAS clinical trial, on-demand IFN-β treatment of asthmatics failed to prevent severe exacerbations.
Objectives: The dynamics of exogenous IFN-β activity were investigated to inform on future clinical indications for this potential anti-viral therapy.
Methods: Monocyte-derived macrophages (MDMs), alveolar macrophages and primary bronchial epithelial cells (PBECs) were isolated from healthy controls and COPD patients and infected with influenza virus either prior to or after IFN-β stimulation. Infection levels were measured by % nucleoprotein 1 positive (NP1+) cells using flow cytometry. Viral RNA shedding and interferon stimulated gene expression were measured by qPCR. 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 %NP1+ cells by 85%, 56% and 66%, respectively (p<0.05). The effect of IFN-β lasted up to 1 week in MDMs and 72 h in PBECs after IFN-β removal; this was similar between health and COPD. Exogenous IFN-β did not induce inflammatory cytokine production by MDMs or PBECs but reduced influenza-induced IL-1β production by PBECs.
Conclusions: In vitro modelling 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.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA5441.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019