title: CXC chemokines and antimicrobial peptides in rhinovirus-induced experimental asthma exacerbations.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: G
authors.initials: G
authors.lastname: Rohde
authors.forename: S D
authors.initials: SD
authors.lastname: Message
authors.forename: J J
authors.initials: JJ
authors.lastname: Haas
authors.forename: T
authors.initials: T
authors.lastname: Kebadze
authors.forename: H
authors.initials: H
authors.lastname: Parker
authors.forename: V
authors.initials: V
authors.lastname: Laza-Stanca
authors.forename: M R
authors.initials: MR
authors.lastname: Khaitov
authors.forename: O M
authors.initials: OM
authors.lastname: Kon
authors.forename: L A
authors.initials: LA
authors.lastname: Stanciu
authors.forename: P
authors.initials: P
authors.lastname: Mallia
authors.forename: M R
authors.initials: MR
authors.lastname: Edwards
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D000293:Adolescent; D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001249:Asthma / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000821:virology; D016022:Case-Control Studies; D019743:Chemokines, CXC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018450:Disease Progression; D053492:Elafin / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010850:Picornaviridae Infections / Q000150:complications*; D012129:Respiratory Function Tests; D012229:Rhinovirus / Q000276:immunology*; D055815:Young Adult
chemical_list: D023181:Antimicrobial Cationic Peptides; D019743:Chemokines, CXC; D053492:Elafin
keywords: airway epithelium; infection control; innate immunity; neutrophil biology; respiratory infection