Author: Rohde, G.; Message, S. D.; Haas, J. J.; Kebadze, T.; Parker, H.; Lazaâ€Stanca, V.; Khaitov, M. R.; Kon, O. M.; Stanciu, L. A.; Mallia, P.; Edwards, M. R.; Johnston, S. L.
Title: CXC chemokines and antimicrobial peptides in rhinovirusâ€induced experimental asthma exacerbations Cord-id: rft22vo8 Document date: 2014_6_23
ID: rft22vo8
Snippet: 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 RVâ€induced asthma exacerbations. OBJECTIVES: We hypothesized that neutrophilâ€related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RVâ€induced exacerbations of asthma. METHODS: Protein levels
Document: 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 RVâ€induced asthma exacerbations. OBJECTIVES: We hypothesized that neutrophilâ€related CXC chemokines and antimicrobial peptides are increased and related to clinical, virologic, and pathologic outcomes in RVâ€induced exacerbations of asthma. METHODS: Protein levels of antimicrobial peptides (SLPI, HNP 1–3, elafin, and LLâ€37) and neutrophil chemokines (CXCL1/GROâ€Î±, CXCL2/GROâ€Î², CXCL5/ENAâ€78, CXCL6/GCPâ€2, CXCL7/NAPâ€2, and CXCL8/ILâ€8) were determined in bronchoalveolar lavage (BAL) fluid of 10 asthmatics and 15 normal controls taken before, at day four during and 6 weeks postâ€experimental infection. RESULTS: BAL HNP 1–3 and Elafin were higher, CXCL7/NAPâ€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/ILâ€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 ILâ€8 levels. CONCLUSIONS: We propose that RV infection in asthma leads to increased release of CXCL8/ILâ€8, attracting neutrophils into the airways where they release HNP 1–3, which further enhances airway neutrophilia. Strategies to inhibit CXCL8/ILâ€8 may be useful in treatment of virusâ€induced asthma exacerbations.
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