Effect of exogenous interferons on rhinovirus replication and airway inflammatory responses

Abstract

Background: Human rhinoviruses (HRVs) are the most common cause of asthma exacerbations. In airway epithelial cells, the primary site of HRV infection, decreased production of interferons (IFNs) may result in greater susceptibility to HRV and worsened symptoms. Thus, exogenous IFN could supplement the innate immune response and provide a treatment for virus-induced asthma exacerbations. Furthermore, the effects of exogenous IFN could be type specific in part because of the cellular distribution of type 1 and type 2 IFN receptors.

Objective: To investigate the effects of exogenous IFNs on HRV replication in bronchial epithelial cells.

Methods: Frozen stocks of primary human bronchial epithelial cells from healthy donors were cultured in monolayers; pretreated (24 hours) with 0.1-ng/mL, 1-ng/mL, or 10-ng/mL doses of IFN-α, -β, -λ1, or -λ2; and infected with HRV-1A. Viral replication was quantified using real-time reverse transcription-polymerase chain reaction, and cytokine and chemokine secretion 24 hours after infection was measured by multiplex enzyme-linked immunosorbent assay.

Results: Compared with untreated samples, IFN-α, IFN-β, IFN-λ1, and IFN-λ2 (0.1 ng/mL) significantly reduced HRV replication after high- (P < .02) and low-dose inoculation (P < .05). Similar effects were seen in 1-ng/mL and 10-ng/mL doses of IFN, where HRV replication was significantly decreased in both high- (P < .001) and low-dose inoculation (P < .001). Treatment with IFNs also enhanced HRV-induced IFN-γ-induced protein 10 secretion (P < .001). Finally, treatment with either IFN-λ1 or IFN-λ2 significantly increased HRV-induced secretion of RANTES (regulated on activation, normal T-expressed, and presumably secreted) (P < .05) but not IL-1β or vascular endothelial growth factor.

Conclusion: These findings suggest that exogenous IFNs, IFN-λ1 in particular, warrant further study as a potential therapy for virus-induced asthma exacerbations.