title: Vitamin D analogs decrease in vitro secretion of RANTES and enhance the effect of budesonide.
abstract: OBJECTIVE
  Eosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts.
  
  
  METHODS
  NP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10(-7)M to 10(-4)M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method.
  
  
  RESULTS
  The highest calcitriol concentration (10(-4)M) as well as tacalcitol at 10(-5)M and 10(-4)M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively).
  
  
  CONCLUSIONS
  Active VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.
authors.affiliation: Department of Otolaryngology, Wroclaw Medical University, Wroclaw, Poland. raucedo@wp.pl
authors.forename: M
authors.initials: M
authors.lastname: Fraczek
authors.forename: B
authors.initials: B
authors.lastname: Rostkowska-Nadolska
authors.forename: D
authors.initials: D
authors.lastname: Kusmierz
authors.forename: A
authors.initials: A
authors.lastname: Zielinska
authors.forename: J
authors.initials: J
authors.lastname: Rok
authors.forename: E
authors.initials: E
authors.lastname: Sliupkas-Dyrda
authors.forename: A
authors.initials: A
authors.lastname: Grzanka
authors.forename: T
authors.initials: T
authors.lastname: Krecicki
authors.forename: M
authors.initials: M
authors.lastname: Latocha
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage*; D002117:Calcitriol / Q000008:administration & dosage; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis*; D004100:Dihydroxycholecalciferols / Q000008:administration & dosage; D004357:Drug Synergism; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D009298:Nasal Polyps / Q000188:drug therapy* / Q000276:immunology; D012220:Rhinitis / Q000188:drug therapy / Q000276:immunology; D012852:Sinusitis / Q000188:drug therapy / Q000276:immunology; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000893:Anti-Inflammatory Agents; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D004100:Dihydroxycholecalciferols; D005938:Glucocorticoids; D014807:Vitamin D; D019819:Budesonide; C023850:1 alpha,24-dihydroxyvitamin D3; D002117:Calcitriol