title: Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients.
abstract: OBJECTIVE
  Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis.
  
  
  METHODS
  We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium.
  
  
  RESULTS
  After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed.
  
  
  CONCLUSIONS
  These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.
authors.affiliation: Department of Rheumatology, Military Medical Academy, Belgrade, Yugoslavia.
authors.forename: Z
authors.initials: Z
authors.lastname: Andjelkovic
authors.forename: J
authors.initials: J
authors.lastname: Vojinovic
authors.forename: N
authors.initials: N
authors.lastname: Pejnovic
authors.forename: M
authors.initials: M
authors.lastname: Popovic
authors.forename: A
authors.initials: A
authors.lastname: Dujic
authors.forename: D
authors.initials: D
authors.lastname: Mitrovic
authors.forename: L
authors.initials: L
authors.lastname: Pavlica
authors.forename: D
authors.initials: D
authors.lastname: Stefanovic
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D002112:Calcifediol / Q000008:administration & dosage*; D002118:Calcium / Q000097:blood / Q000652:urine; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D018501:Antirheumatic Agents; D010835:Phytohemagglutinins; D002112:Calcifediol; D002118:Calcium