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.