Dynamics of IFN-β Responses during Respiratory Viral Infection. Insights for Therapeutic Strategies

• DOI: 10.1164/rccm.201901-0214oc
• Publication Date: 2019-08-28T21:35:31Z
• Authors: Alastair Watson; C. Mirella Spalluto; Christopher McCrae; Doriana Cellura; Hannah Burke; Danen Cunoosamy; Anna Freeman; Alex Hicks; Michael Hühn; Kristoffer Ostridge; Karl J. Staples; Outi Vaarala; Tom Wilkinson
• Keywords: Mononegavirales

Rationale: Viral infections are major drivers of exacerbations and clinical burden in patients with asthma chronic obstructive pulmonary disease (COPD). IFN-β is a key component the innate immune response to viral infection. To date, studies inhaled treatment have not demonstrated significant effect on exacerbations.Objectives: The dynamics exogenous activity were investigated inform future indications for this potential antiviral therapy.Methods: Monocyte-derived macrophages (MDMs), alveolar macrophages, primary bronchial epithelial cells (PBECs) isolated from healthy control subjects COPD infected influenza virus either prior or after stimulation. Infection levels measured by percentage nucleoprotein 1-positive using flow cytometry. RNA shedding IFN-stimulated gene expression quantitative PCR. Production inflammatory cytokines was MSD.Measurements Main Results: Adding MDMs, PBECs to, but after, infection reduced 85, 56, 66%, respectively (P < 0.05). Inhibition lasted 24 hours removal maintained albeit up 1 week MDMs 72 PBECs; similar between COPD. did induce cytokine production influenza-induced IL-1β PBECs.Conclusions:In vitro modeling highlights intermittent prophylactic doses modulate This provides important insights aid design trials