• Julie A Cakebread, Yunhe Xu, Chris Grainge, Valia Kehagia, Peter H Howarth, Stephen T Holgate, and Donna E Davies.
• Division of Infection, Inflammation and Immunity, University of Southampton School of Medicine and National Institute for Health Research Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, United Kingdom.
• J. Allergy Clin. Immunol. 2011 May 1; 127 (5): 1148-54.e9.

BackgroundRhinoviruses are the major cause of asthma exacerbations. Previous studies suggest that primary bronchial epithelial cells (PBECs) from asthmatic subjects are more susceptible to rhinovirus infection because of deficient IFN-β production. Although augmenting the innate immune response might provide a novel approach for treatment of virus-induced asthma exacerbations, the potential of IFN-β to modulate antiviral and proinflammatory responses in asthmatic epithelium is poorly characterized.ObjectivesWe sought to compare responses of PBECs from nonasthmatic and asthmatic subjects to exogenous IFN-β and test the inflammatory effects of IFN-β in response to rhinovirus infection.MethodsPBECs were treated with IFN-β and infected with a low inoculum of human rhinovirus serotype 1B to simulate a natural viral infection. Expression of interferon-responsive genes and inflammatory responses were analyzed by using reverse transcription-quantitative real-time PCR, cytometric bead arrays, or both; viral titers were assessed by using the 50% tissue culture infection dose.ResultsExpression of IFN-β-stimulated antiviral genes was comparable in PBECs from nonasthmatic or asthmatic donors. Exogenous IFN-β significantly protected PBECs from asthmatic donors against rhinovirus infection by suppressing viral replication. Interferon-inducible protein 10 (IP-10), RANTES, and IL-6 release in response to rhinovirus infection was triggered only in PBECs from asthmatic donors. Although exogenous IFN-β alone stimulated some release of IP-10 (but not IL-6 or RANTES), it significantly reduced rhinovirus-induced IP-10, RANTES, and IL-6 expression when tested in combination with rhinovirus.ConclusionsPBECs from asthmatic donors have a normal antiviral response to exogenous IFN-β. The ability of IFN-β to suppress viral replication suggests that it might limit virus-induced exacerbations by shortening the duration of the inflammatory response.Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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