Mechanisms of asthma and allergic inflammation
IFN-γ–induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations

https://doi.org/10.1016/j.jaci.2007.04.046Get rights and content

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 virus-induced 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-γ–induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-α. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-α 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 (r = −0.8; 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.

Key words

Asthma
rhinovirus
airway inflammation

Abbreviations used

BEC
Bronchial epithelial cell
IP-10
IFN-γ–induced protein 10
LR
Likelihood ratio
NF-κB
Nuclear factor κB
RV-16
Rhinovirus 16
TCID50
Tissue culture infectious dose 50%

Cited by (0)

Supported by the British Medical Association HC Roscoe fellowship and Asthma UK. Dr Wark was funded by the National Health and Medical Research Council of Australia on a Neil Hamilton Fairley traveling fellowship.

Disclosure of potential conflict of interest: P. A. B. Wark has consultant arrangements with AstraZeneca, has a patent licensing arrangement from antivirus therapy for respiratory diseases, and receives grants/research support from Biota Pty, Ltd. S. L. Johnston has consultant arrangements with AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, MedImmune, Merck, Pfizer, Sanofi-Aventis, Schering-Plough, and Synairgen; has patent licensing arrangements for transgenic animal models of HRV with human intercellular adhesion molecule 1 sequences, antivirus therapy for respiratory diseases, and the use of IFN-λ for the treatment and prevention of virally induced exacerbation in asthma and chronic pulmonary obstructive disease; and receives grants/research support from AstraZeneca, Centocor, GlaxoSmithKline, Pfizer, and Merck. S. T. Holgate has consultant arrangements with Synairgen, Novartis, Merck, Cambridge Antibody Technology, Almiral, and Rotta; owns stock in Synairgen; receives grant support from Novartis and UCB; and is on the speakers' bureau for Novartis and Merck. The rest of the authors have declared that they have no conflict of interest.

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