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

Cakebread, Julie A., Xu, Yunhe, Grainge, Chris, Kehagia, Valia, Howarth, Peter H., Holgate, Stephen T. and Davies, Donna E. (2011) Exogenous IFN-? has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus. Journal of Allergy and Clinical Immunology, 127 (5), 1148-1154.e9. (doi:10.1016/j.jaci.2011.01.023). (PMID:21329968)

Abstract

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-? production. Although augmenting the innate immune response might provide a novel approach for treatment of virus-induced asthma exacerbations, the potential of IFN-? 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-? and test the inflammatory effects of IFN-? in response to rhinovirus infection.

Methods: PBECs were treated with IFN-? 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-?–stimulated antiviral genes was comparable in PBECs from nonasthmatic or asthmatic donors. Exogenous IFN-? 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-? 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-?. The ability of IFN-? to suppress viral replication suggests that it might limit virus-induced exacerbations by shortening the duration of the inflammatory response.

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Contributors

Author: Donna E. Davies

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