The Journal of Allergy and Clinical Immunology
Volume 120, Issue 3 , Pages 586-593, September 2007

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

  • Peter A.B. Wark, BMed, PhD

      Affiliations

    • Brooke Laboratories, University of Southampton, Southampton, United Kingdom
    • Department of Respiratory and Sleep Medicine, John Hunter Hospital, University of Newcastle, Newcastle, Australia
    • Corresponding Author InformationReprint requests: Peter A. B. Wark, BMed, PhD, Department of Respiratory and Sleep Medicine, John Hunter Hospital, Locked Bag 1 HRMC, NSW 2310, Australia.
    • ,
  • Fabio Bucchieri, MD

      Affiliations

    • Department of Experimental Medicine, Human Anatomy Division, University of Palermo, Palermo, Italy
    • ,
  • Sebastian L. Johnston, MD, PhD

      Affiliations

    • Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom
    • ,
  • Peter G. Gibson, MBBS

      Affiliations

    • Department of Respiratory and Sleep Medicine, John Hunter Hospital, University of Newcastle, Newcastle, Australia
    • ,
  • Lynnsey Hamilton, BSci, PhD

      Affiliations

    • Brooke Laboratories, University of Southampton, Southampton, United Kingdom
    • ,
  • Joanna Mimica

      Affiliations

    • Department of Respiratory and Sleep Medicine, John Hunter Hospital, University of Newcastle, Newcastle, Australia
    • ,
  • Giovanni Zummo, MD

      Affiliations

    • Department of Experimental Medicine, Human Anatomy Division, University of Palermo, Palermo, Italy
    • ,
  • Stephen T. Holgate, FRCP

      Affiliations

    • Brooke Laboratories, University of Southampton, Southampton, United Kingdom
    • ,
  • John Attia, MD, PhD

      Affiliations

    • Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, Australia
    • ,
  • Ammarin Thakkinstian, MD

      Affiliations

    • Centre for Clinical Epidemiology and Biostatistics, University of Newcastle, Newcastle, Australia
    • Clinical Epidemiology Unit, Mahidol University, Bangkok, Thailand
    • ,
  • Donna E. Davies, PhD

      Affiliations

    • Brooke Laboratories, University of Southampton, Southampton, United Kingdom

Received 16 February 2007; received in revised form 18 April 2007; accepted 19 April 2007. published online 12 July 2007.

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%

 

 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.

PII: S0091-6749(07)01025-1

doi:10.1016/j.jaci.2007.04.046

The Journal of Allergy and Clinical Immunology
Volume 120, Issue 3 , Pages 586-593, September 2007

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