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

G. Rohde, S.D. Message, J.J. Haas, T. Kebadze, H. Parker, V. Laza-Stanca, M.R. Khaitov, O.M. Kon, L.A. Stanciu, P. Mallia, M.R. Edwards, S. L. Johnston

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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-alpha, CXCL2/GRO-beta, 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.
Original languageEnglish
Pages (from-to)930-939
Number of pages10
JournalClinical and Experimental Allergy
Volume44
Issue number7
DOIs
Publication statusPublished - Jul 2014

Keywords

  • airway epithelium
  • infection control
  • innate immunity
  • neutrophil biology
  • respiratory infection
  • VIRUS-INDUCED ASTHMA
  • DENDRITIC CELLS
  • ALPHA-DEFENSINS
  • 16 INFECTION
  • INFLAMMATION
  • SEVERITY
  • DISEASE
  • ADULTS
  • NEUTROPHILS
  • MODULATION

Cite this

Rohde, G., Message, S. D., Haas, J. J., Kebadze, T., Parker, H., Laza-Stanca, V., Khaitov, M. R., Kon, O. M., Stanciu, L. A., Mallia, P., Edwards, M. R., & Johnston, S. L. (2014). CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations. Clinical and Experimental Allergy, 44(7), 930-939. https://doi.org/10.1111/cea.12313