CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations

Authors

  • G. Rohde,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
    2. Department of Respiratory Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands
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  • S. D. Message,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
    2. Imperial College Healthcare NHS Trust, London, UK
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  • J. J. Haas,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
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  • T. Kebadze,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
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  • H. Parker,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
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  • V. Laza-Stanca,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
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  • M. R. Khaitov,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
    2. State National Center Institute of Immunology, Federal Medicobiological Agency of Russia, Moscow, Russia
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  • O. M. Kon,

    1. Imperial College Healthcare NHS Trust, London, UK
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  • L. A. Stanciu,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
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  • P. Mallia,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
    2. Imperial College Healthcare NHS Trust, London, UK
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  • M. R. Edwards,

    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
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  • S. L. Johnston

    Corresponding author
    1. Department of Respiratory Medicine, National Heart and Lung Institute, MRC and Asthma UK Centre in Allergic Mechanisms of Asthma & Centre for Respiratory Infection, Imperial College London, London, UK
    2. Imperial College Healthcare NHS Trust, London, UK
    • Correspondence:

      Sebastian L. Johnston, Professor of Respiratory Medicine, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK.

      E-mail: s.johnston@imperial.ac.uk

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  • The copyright line for this article was changed on 30 March 2015 after original online publication.

Summary

Rationale

Rhinoviruses (RVs) are the major triggers of asthma exacerbations. We have shown previously that lower respiratory tract symptoms, airflow obstruction, and neutrophilic airway inflammation were increased in experimental RV-induced asthma exacerbations.

Objectives

We hypothesized that neutrophil-related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RV-induced exacerbations of asthma.

Methods

Protein levels of antimicrobial peptides (SLPI, HNP 1–3, elafin, and LL-37) and neutrophil chemokines (CXCL1/GRO-α, CXCL2/GRO-β, CXCL5/ENA-78, CXCL6/GCP-2, CXCL7/NAP-2, and CXCL8/IL-8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks post-experimental infection.

Results

BAL HNP 1–3 and Elafin were higher, CXCL7/NAP-2 was lower in asthmatics compared with controls at day 4 (P = 0.035, P = 0.048, and P = 0.025, respectively). BAL HNP 1–3 and CXCL8/IL-8 were increased during infection (P = 0.003 and P = 0.011, respectively). There was a trend to increased BAL neutrophils at day 4 compared with baseline (P = 0.076). BAL HNP 1–3 was positively correlated with BAL neutrophil numbers at day 4. There were no correlations between clinical parameters and HNP1–3 or IL-8 levels.

Conclusions

We propose that RV infection in asthma leads to increased release of CXCL8/IL-8, attracting neutrophils into the airways where they release HNP 1–3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/IL-8 may be useful in treatment of virus-induced asthma exacerbations.

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