title: Vitamin D deficiency impacts on expression of toll-like receptor-2 and cytokine profile: a pilot study.
abstract: BACKGROUND
  Vitamin D is believed to play an important role outside the endocrine system in the regulation of the immune system, and in cellular proliferation and differentiation. The aim of the study was to investigate the impact of vitamin D levels on innate immunity.
  
  
  METHODS
  Participants for this prospective, longitudinal study were recruited amongst otherwise healthy staff of a large hospital in Victoria, Australia. Those fulfilling the inclusion criteria, including a vitamin D level of <50 nmol/L, were supplemented. Using flow cytometry, expression of the innate immune receptors TLR2, TLR4 and CD86 was measured on peripheral blood mononuclear cells (PBMCs) collected prior to vitamin D treatment and then at 1 and 3 months. Additonally, PBMCs at each timepoint were stimulated with specific TLR ligands and resultant supernatants were assayed for the cytokines TNFα, IL-6, IFN-α and IP-10.
  
  
  RESULTS
  In participants whose vitamin D level was >100 nmol/L post supplementation (n=11), TLR2 expression on PBMCs increased significantly, with no change noted in TLR4 or CD86 expression. Stimulation of vitamin D deficient samples with TLR ligands produced a number of proinflammatory cytokines, which were significantly reduced upon vitamin D normalisation. In patients whose levels returned to a deficient level at 3 months despite ongoing low-level supplementation, an increase in the pro-inflamamtory state returned. This suggests that vitamin D may play an important role in ensuring an appropriate baseline pro-inflammatory state.
  
  
  CONCLUSIONS
  This ex-vivo pilot study adds clinical evidence supporting a possibly important role for vitamin D in innate immunity. If confirmed, this unique clinical study has potentially significant implications for the treatment of a variety of inflammatory conditions, where achieving optimal vitamin D levels may help reduce inflammation.
authors.affiliation: Department of Infectious Diseases, Southern Health, Clayton Rd, Clayton, Victoria, Australia.
authors.forename: Samar
authors.initials: S
authors.lastname: Ojaimi
authors.forename: Narelle A
authors.initials: NA
authors.lastname: Skinner
authors.forename: Boyd Jg
authors.initials: BJ
authors.lastname: Strauss
authors.forename: Vijaya
authors.initials: V
authors.lastname: Sundararajan
authors.forename: Ian
authors.initials: I
authors.lastname: Woolley
authors.forename: Kumar
authors.initials: K
authors.lastname: Visvanathan
mesh_terms: D000328:Adult; D002454:Cell Differentiation; D049109:Cell Proliferation; D054357:Chemokine CXCL10 / Q000276:immunology; D016207:Cytokines / Q000276:immunology*; D019587:Dietary Supplements; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D016898:Interferon-alpha / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008024:Ligands; D008137:Longitudinal Studies; D008297:Male; D010865:Pilot Projects; D011446:Prospective Studies; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood; D014808:Vitamin D Deficiency / Q000378:metabolism*
chemical_list: D054357:Chemokine CXCL10; D016207:Cytokines; D016898:Interferon-alpha; D015850:Interleukin-6; D008024:Ligands; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D014807:Vitamin D