CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations
Article first published online: 23 JUN 2014
© 2014 John Wiley & Sons Ltd
Clinical & Experimental Allergy
Volume 44, Issue 7, pages 930–939, July 2014
How to Cite
Clinical & Experimental Allergy, 2014 (44) 930–939., , , , , , , , , , and ,
- Issue published online: 23 JUN 2014
- Article first published online: 23 JUN 2014
- Accepted manuscript online: 26 MAR 2014 08:55AM EST
- Manuscript Accepted: 10 FEB 2014
- Manuscript Revised: 28 JAN 2014
- Manuscript Received: 10 JAN 2013
- European Respiratory Society. Grant Number: 243
- Medical Research Council
- British Medical Association HC Roscoe
- Asthma UK. Grant Numbers: 02/027, 05/067
- British Lung Foundation/Severin Wunderman Family Foundation. Grant Number: 00/02
- Wellcome Trust. Grant Numbers: 063717, 083567/Z/07/Z
- National Institute for Health Research
- NIHR Biomedical Research Centre
- airway epithelium;
- infection control;
- innate immunity;
- neutrophil biology;
- respiratory infection
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.
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.
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.
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.
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.