title: Effect of desloratadine on epithelial cell granulocyte-macrophage colony-stimulating factor secretion and eosinophil survival.
abstract: BACKGROUND
  Second-generation antihistamines are H(1) receptor antagonists and may have additional anti-inflammatory effects.
  
  
  OBJECTIVE
  The aims of the study were to evaluate the effect of desloratadine (DL) on cytokine secretion by epithelial cells from both nasal mucosa (NM) and polyps (NP), and on eosinophil survival primed by epithelial cell secretions.
  
  
  METHODS
  Epithelial cells were cultured and stimulated with fetal bovine serum (FBS), IL-1beta or TNF-alpha with and without DL for 24 h. Culture supernatant cytokines concentration were measured by ELISA. Peripheral blood eosinophils were incubated with human epithelial cell conditioned media (HECM) and DL. Eosinophil survival was assessed by Trypan blue dye exclusion. Results are expressed as mean+/-SEM of cytokine concentration (pg/mL) or eosinophil survival index (%).
  
  
  RESULTS
  FBS increased granulocyte-macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), IL-6, IL-8, and TGF-beta(1) secretion in epithelial cell cultures from both NM and NP. Only GM-CSF secretion was significantly (P<0.05) inhibited by a dose-response of DL compared with positive controls, in both NM (10(-5) m: 125+/-36 pg/mL, 10(-6) m: 95+/-22 pg/mL vs. control: 256+/-91 pg/mL, n=6) and NP (10(-5) m: 80+/-29 pg/mL, 10(-6) m: 109+/-45 pg/mL vs. control: 333+/-212 pg/mL, n=6). DL also showed an inhibitory effect on HECM-induced eosinophil survival from both NM and NP. At 72 h, DL significantly (P<0.01) inhibited eosinophil survival induced by HECM from NM (10(-5) m: 19.9+/-5.5%, n=9; 10(-6) m: 28.7+/-7.7%, n=9) and NP (10(-5) m: 6.2+/-2.8%, n=11) compared with HECM alone (NM: 42.1+/-7.3%; NP: 45.3+/-8.1%).
  
  
  CONCLUSIONS
  The inhibitory effects of DL on epithelial cell GM-CSF secretion and on eosinophil survival induced by epithelial cell secretions, suggest that this H(1) antagonist may regulate eosinophil inflammation in upper airways.
authors.affiliation: IDIBAPS, Rhinology Unit, ENT Department, Hospital Clinic, Deparmtent of Medicine, Universitat de Barcelona, Barcelona, Catalonia, Spain. jmullol@clinic.ub.es
authors.forename: J
authors.initials: J
authors.lastname: Mullol
authors.forename: J
authors.initials: J
authors.lastname: Roca-Ferrer
authors.forename: I
authors.initials: I
authors.lastname: Alobid
authors.forename: L
authors.initials: L
authors.lastname: Pujols
authors.forename: A
authors.initials: A
authors.lastname: Valero
authors.forename: A
authors.initials: A
authors.lastname: Xaubet
authors.forename: M
authors.initials: M
authors.lastname: Bernal-Sprekelsen
authors.forename: C
authors.initials: C
authors.lastname: Picado
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000032:analysis; D019742:Chemokines, CC / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D004804:Eosinophils / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis*; D006634:Histamine H1 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015848:Interleukin-5 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000276:immunology*; D009298:Nasal Polyps / Q000188:drug therapy / Q000276:immunology*; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: C515456:CCL11 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D019742:Chemokines, CC; D006634:Histamine H1 Antagonists; D015848:Interleukin-5; D015850:Interleukin-6; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D017336:Loratadine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; C121345:desloratadine