Abstract
Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma and COPD. IFN-ß is essential for controlling the infection and spread of viruses such as influenza.
Objectives: The dynamics of IFN-ß 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-ß 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-ß 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-ß lasted up to 1 week in MDMs and 72 h in PBECs after IFN-ß removal; this was similar between health and COPD. Exogenous IFN-ß did not induce inflammatory cytokine production by MDMs or PBECs but reduced influenza-induced IL-1ß production by PBECs.
Conclusions: In vitro modelling of IFN-ß dynamics highlights the potential for intermittent prophylactic doses of exogenous IFN-ß to modulate viral infection. This generates novel insights to aid the future design of clinical trials of IFN-ß in asthma and COPD.
Footnotes
Cite this article as: ERJ Open Research 2019; 5 : Suppl. 2, PP126.
This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this conference is available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2019