title: Differential cytokine, chemokine and growth factor expression in phenotypes of chronic lung allograft dysfunction.
abstract: BACKGROUND
  Chronic lung allograft dysfunction is a heterogeneous entity limiting long-term survival after lung transplantation. Different clinical phenotypes (bronchiolitis obliterans syndrome [BOS]-neutrophilic BOS-restrictive allograft syndrome [RAS]) have been identified but the mechanisms remain elusive.
  
  
  METHODS
  In this study, we measured 34 different cytokines, chemokines, and growth factors in bronchoalveolar lavage fluid of 20 stable patients, 20 patients suffering from non-neutrophilic BOS, 17 from neutrophilic BOS, and 20 from RAS using classic enzyme-linked immunosorbent assay and multiplex technology.
  
  
  RESULTS
  Total cell count and % neutrophils were elevated in neutrophilic BOS and RAS compared to stable and non-neutrophilic BOS patients, whereas also the % eosinophils was elevated at diagnosis of RAS. Levels of interleukin (IL)-1β (P<0.01), IL-1Rα (P<0.001), IL-6 (P<0.001), IL-8/CXCL8 (P<0.001), IP-10/CXCL10 (P<0.05), MCP-1/CCL2 (P<0.05), macrophage inflammatory protein (MIP)-1α/CCL3 (P<0.001), MIP-1β/CCL4, and vascular endothelial growth factor (VEGF; P<0.05) were differentially regulated in RAS compared to stable, whereas in neutrophilic BOS IL-1β (P<0.001), IL-1Rα (P<0.01), IL-7 (P<0.05), IL-8/CXCL8 (P<0.001), MCP-3/CXCCL7 (P<0.05) and MIP-1α/CCL-3 (P<0.05) were significantly upregulated compared to stable patients. We could not detect any differences between non-neutrophilic BOS and stable patients. Interestingly, bronchoalveolar lavage IL-6, interferon gamma-induced protein (IP)-10/CXCL10 and interferon-inducible T-cell alpha chemoattractant/chemokine (C-X-C motif) ligand 11 (ITAC/CXCL10) were associated with survival after diagnosis in RAS patients.
  
  
  CONCLUSIONS
  There were major differences in cytokine and chemokine expression in our different study groups. Especially IL-6, but also IP-10/CXCL10, and VEGF may be interesting mediators in RAS.
authors: 1 Department of Clinical and Experimental Medicine, Laboratory of Pneumology, Lung Transplant Unit, Katholieke Universiteit Leuven and University Hospital Gasthuisberg, Leuven, Belgium. 2 Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
authors: Stijn E
authors: SE
authors: Verleden
authors: David
authors: D
authors: Ruttens
authors: Robin
authors: R
authors: Vos
authors: Elly
authors: E
authors: Vandermeulen
authors: Eva
authors: E
authors: Moelants
authors: Anneleen
authors: A
authors: Mortier
authors: Dirk E
authors: DE
authors: Van Raemdonck
authors: Paul
authors: P
authors: Proost
authors: Dominique
authors: D
authors: Schols
authors: Geert M
authors: GM
authors: Verleden
authors: Bart M
authors: BM
authors: Vanaudenaerde
mesh_terms: D000328:Adult; D064591:Allografts; D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000145:classification / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D018925:Chemokines / Q000032:analysis*; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D007958:Leukocyte Count; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010641:Phenotype; D011379:Prognosis; D016016:Proportional Hazards Models; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins