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 COPD. IFN-s is essential for controlling the infection and spread of viruses such as influenza. Objectives: The dynamics of IFN-s 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-s stimulation. Infection levels were measured by %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-s to MDMs, alveolar macrophages and PBECs prior to, but not after, infection reduced %NP1+ cells by 85%, 56% and 66%, respectively (p Conclusions: In vitro modelling of IFN-s dynamics highlights the potential for intermittent prophylactic doses of exogenous IFN-s to modulate viral infection. This generates novel insights to aid the future design of clinical trials of IFN-s in asthma and COPD.