title: Oral vitamin D3 supplementation reduces monocyte-derived dendritic cell maturation and cytokine production in Crohn's disease patients.
abstract: BACKGROUND
  Low serum vitamin D levels may provoke or aggravate Crohn's disease (CrD). Vitamin D3 is a well-known immune modulator that affects immune functions in vitro and may prevent CrD flares. Dendritic cells (DC) are key mediators of vitamin D3 effects. In this study, we describe changes in monocyte-derived DC (mo-DC) maturation marker expression and cytokine production following 26 weeks of oral vitamin D3 supplementation in CrD patients.
  
  
  METHODS
  Ten CrD patients who had increased serum 25-hydroxy vitamin D levels after oral vitamin D3 and calcium treatment and ten seasonally matched placebo-treated patients were selected for this study. Mo-DC were generated before and after the 26 weeks and induced to mature upon lipopolysaccharide (LPS) stimulation. Maturation marker expression and cytokine production were analysed. Mo-DC function was analysed in a mixed leucocyte reaction (MLR).
  
  
  RESULTS
  Compared with baseline values, LPS-matured mo-DC exhibited reduced expression of CD80 and reduced production of the cytokines IL-10, IL-1β, and IL-6 following 26 weeks of oral vitamin D3 supplementation. Mo-DC performance in an allogeneic MLR was unchanged after vitamin D3 supplementation. Treatment with the placebo did not affect maturation markers, cytokine production, or the MLR.
  
  
  CONCLUSIONS
  Vitamin D3 treatment in CrD patients led to hypo-responsive LPS-stimulated mo-DC. This finding indicates that vitamin D3 levels have an impact on the monocytic precursors of mo-DC in vivo and may explain the positive effects of vitamin D3 supplementation on CrD patients. Alternatively, CrD patients with high serum vitamin D3 levels may represent a subgroup with low disease activity.
authors.affiliation: Gastro-Immuno Research Laboratory (GIRL), Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus, Denmark, larsbart@rm.dk.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Bartels
authors.forename: Mia
authors.initials: M
authors.lastname: Bendix
authors.forename: Christian L
authors.initials: CL
authors.lastname: Hvas
authors.forename: Søren P
authors.initials: SP
authors.lastname: Jørgensen
authors.forename: Jørgen
authors.initials: J
authors.lastname: Agnholt
authors.forename: Ralf
authors.initials: R
authors.lastname: Agger
authors.forename: Jens F
authors.initials: JF
authors.lastname: Dahlerup
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002118:Calcium / Q000008:administration & dosage; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D055815:Young Adult
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D; D002118:Calcium