IFN-?–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations

Wark, Peter A.B., Bucchieri, Fabio, Johnston, Sebastian L., Gibson, Peter G., Hamilton, Lynnsey, Mimica, Joanna, Zummo, Giovanni, Holgate, Stephen T., Attia, John, Thakkinstian, Ammarin and Davies, Donna E. (2007) IFN-?–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations. Journal of Allergy and Clinical Immunology, 120 (3), 586-593. (doi:10.1016/j.jaci.2007.04.046).

Abstract

Background: Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations.
Objective: We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virusinduced asthma.
Methods: BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments.
Results: IFN-g–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-a. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-a but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non–virus-induced acute asthma, P <.01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 [95% CI, 3.9-100.3]). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction (r520.8; P < .01).
Conclusions: IP-10 release is specific to acute virus-induced asthma.
Clinical implications: Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.

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Contributors

Author: Donna E. Davies

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