Exogenous IFN-β has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus

Background: Rhinoviruses 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-beta production. Although augmenting the innate immune response might provide a novel approach for treatment of virus-induced asthma exacerbations, the potential of IFN-beta to modulate antiviral and proinflammatory responses in asthmatic epithelium is poorly characterized. Objectives: We sought to compare responses of PBECs from nonasthmatic and asthmatic subjects to exogenous IFN-beta and test the inflammatory effects of IFN-beta in response to rhinovirus infection. Methods: PBECs were treated with IFN-beta 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. Results: Expression of IFN-beta-stimulated antiviral genes was comparable in PBECs from nonasthmatic or asthmatic donors. Exogenous IFN-beta 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-beta 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. Conclusions: PBECs from asthmatic donors have a normal antiviral response to exogenous IFN-beta. The ability of IFN-beta to suppress viral replication suggests that it might limit virus-induced exacerbations by shortening the duration of the inflammatory response. (J Allergy Clin Immunol 2011;127:1148-54.)