title: Systemic and exhaled cytokine and chemokine profiles are associated with the development of bronchiolitis obliterans syndrome.
abstract: BACKGROUND
  The mechanisms that lead to the fibrotic obliteration in bronchiolitis obliterans syndrome (BOS) may involve the interactions between T-helper (Th)1 and Th2 cytokines. The aim of this study is to determine the Th1 and Th2 cytokine and chemokine profiles in serum and exhaled breath condensate (EBC) in lung transplant recipients and to assess their usefulness as biomarkers to predict the development of BOS.
  
  
  METHODS
  Serum and EBC from 10 patients with BOS (BOS(pos)) and 10 patients without BOS (BOS(neg)), matched for clinical and demographic variables, were analyzed with a multiplex immunoassay to measure a panel of 27 cytokines and chemokines.
  
  
  RESULTS
  The pro-inflammatory cytokines in serum were elevated in lung transplant recipients compared with controls. BOS(pos) patients had significantly lower concentrations of interleukin (IL)-4, IL-13, and vascular endothelial growth factor (VEGF) compared with BOS(neg) patients. The concentration of IL-5, however, was significantly higher in BOS(pos) patients. Levels of IL-4 and IL-5 were hardly detectable in EBC. IL-13 and VEGF, both decreased in serum in BOS(pos) patients, were also decreased in EBC in BOS(pos) patients compared with BOS(neg) patients. Longitudinal analysis of cytokines and chemokines in serum and EBC from the time of lung transplantation onwards did not reveal significant trends in cytokines and chemokines that preceded the diagnosis of BOS.
  
  
  CONCLUSIONS
  Levels of pro-inflammatory cytokines were increased in lung transplant recipients compared with controls. From the moment of transplantation onwards, there is a different pattern of Th2 cytokines in serum in BOS(pos) patients than in BOS(neg) patients.
authors.affiliation: Centre of Interstitial Lung Diseases, Department of Pulmonology, St Antonius Hospital, The Netherlands.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Kastelijn
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Coline H M
authors.initials: CH
authors.lastname: Van Moorsel
authors.forename: Pieter
authors.initials: P
authors.lastname: Zanen
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Kwakkel-van Erp
authors.forename: Ed A
authors.initials: EA
authors.lastname: Van De Graaf
authors.forename: Diana A
authors.initials: DA
authors.lastname: Van Kessel
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.forename: Jules M M
authors.initials: JM
authors.lastname: Van Den Bosch
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001944:Breath Tests; D001989:Bronchiolitis Obliterans / Q000175:diagnosis*; D018925:Chemokines / Q000032:analysis / Q000097:blood*; D003550:Cystic Fibrosis / Q000601:surgery; D016207:Cytokines / Q000032:analysis / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D006133:Growth Substances / Q000032:analysis / Q000097:blood; D016041:Heart-Lung Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007378:Interleukins / Q000032:analysis / Q000097:blood; D016040:Lung Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000601:surgery; D012016:Reference Values; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D006133:Growth Substances; D007166:Immunosuppressive Agents; D007378:Interleukins