Abstract
SummaryRationaleRhinoviruses (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.ObjectivesWe 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.MethodsProtein 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.ConclusionsWe 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.
Highlights
Patients with atopic asthma are more susceptible to lower respiratory tract (LRT) infections and have more severe and longer-lasting rhinovirus (RV)-induced LRT symptoms than healthy individuals [1]
We have investigated the effect of RV infection on the expression of CXC chemokines and antimicrobial peptides in a human experimental model of RV-induced asthma exacerbation
In accordance with Turner et al [18], that the neutrophil-attracting chemokine CXCL8/IL-8 is significantly increased in asthmatics compared with normal controls
Summary
Patients with atopic asthma are more susceptible to lower respiratory tract (LRT) infections and have more severe and longer-lasting rhinovirus (RV)-induced LRT symptoms than healthy individuals [1]. Virus infections of the respiratory tract are frequently associated with asthma exacerbations, with RVs as the predominant viruses [2, 3]. RVs directly infect the lower airways [4] resulting in increased lower respiratory symptoms, reductions in lung function, bronchial inflammation, and augmented airway hyperresponsiveness in asthmatic compared with normal subjects [5]. It has been hypothesized that human rhinovirus infections should increase levels of a-defensins in the airways [10], as they lead to marked neutrophil infiltration and degranulation in the airways [11] which are associated with clinical severity of virus-induced asthma [5, 12]. There have been no reports directly measuring defensins in the airways of subjects with virus-induced asthma so far
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