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Clin Exp Allergy. 2014 Jul;44(7):930-9. doi: 10.1111/cea.12313.

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

Author information

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; Department of Respiratory Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Abstract

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.

KEYWORDS:

airway epithelium; infection control; innate immunity; neutrophil biology; respiratory infection

PMID:
24673807
PMCID:
PMC4403958
DOI:
10.1111/cea.12313
[Indexed for MEDLINE]
Free PMC Article
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