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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antimicrobial Cationic Peptides / metabolism*
  • Asthma / diagnosis
  • Asthma / etiology*
  • Asthma / metabolism*
  • Asthma / physiopathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Bronchoalveolar Lavage Fluid / virology
  • Case-Control Studies
  • Chemokines, CXC / metabolism*
  • Chemotaxis, Leukocyte / immunology
  • Disease Progression
  • Elafin / metabolism
  • Female
  • Humans
  • Male
  • Neutrophils / immunology
  • Picornaviridae Infections / complications*
  • Respiratory Function Tests
  • Rhinovirus / immunology*
  • Young Adult


  • Antimicrobial Cationic Peptides
  • Chemokines, CXC
  • Elafin