title: IFN-gamma-induced protein 10 is a novel biomarker of rhinovirus-induced asthma exacerbations.
abstract: BACKGROUND
  Rhinovirus-induced acute asthma is the most frequent trigger for asthma exacerbations.
  
  
  OBJECTIVE
  We assessed which inflammatory mediators were released from bronchial epithelial cells (BECs) after infection with rhinovirus and then determined whether they were also present in subjects with acute virus-induced asthma, with the aim to identify a biomarker or biomarkers for acute virus-induced asthma.
  
  
  METHODS
  BECs were obtained from bronchial brushings of steroid-naive asthmatic subjects and healthy nonatopic control subjects. Cells were infected with rhinovirus 16. Inflammatory mediators were measured by means of flow cytometry with a cytometric bead array. Subjects with acute asthma and virus infection were recruited; they were characterized clinically by using lung function tests and had blood taken to measure the inflammatory mediators identified as important by the BEC experiments.
  
  
  RESULTS
  IFN-gamma-induced protein 10 (IP-10) and RANTES were released in the greatest quantities, followed by IL-6, IL-8, and TNF-alpha. Dexamethasone treatment of BECs only partially suppressed IP-10 and TNF-alpha but was more effective at suppressing RANTES, IL-6, and IL-8. In acute clinical asthma serum IP-10 levels were increased to a greater extent in those with acute virus-induced asthma (median of 604 pg/mL compared with 167 pg/mL in those with non-virus-induced acute asthma, P < .01). Increased serum IP-10 levels were predictive of virus-induced asthma (odds ratio, 44.3 [95% CI, 3.9-100.3]). Increased serum IP-10 levels were strongly associated with more severe airflow obstruction (r = -0.8; P < .01).
  
  
  CONCLUSIONS
  IP-10 release is specific to acute virus-induced asthma.
  
  
  CONCLUSIONS
  Measurement of serum IP-10 could be used to predict a viral trigger to acute asthma.
authors.affiliation: Brooke Laboratories, University of Southampton, Southampton, United Kingdom. peter.wark@hnehealth.nsw.gov.au
authors.forename: Peter A B
authors.initials: PA
authors.lastname: Wark
authors.forename: Fabio
authors.initials: F
authors.lastname: Bucchieri
authors.forename: Sebastian L
authors.initials: SL
authors.lastname: Johnston
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
authors.forename: Lynnsey
authors.initials: L
authors.lastname: Hamilton
authors.forename: Joanna
authors.initials: J
authors.lastname: Mimica
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zummo
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Holgate
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.forename: Donna E
authors.initials: DE
authors.lastname: Davies
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000097:blood* / Q000821:virology*; D015415:Biomarkers / Q000097:blood*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D008875:Middle Aged; D010850:Picornaviridae Infections / Q000150:complications*; D012229:Rhinovirus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C114753:CXCL10 protein, human; D018946:Chemokine CCL5; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone