title: Adjuvant treatment of patients with antineutrophil cytoplasmic antibody-associated vasculitis with vitamins E and C reduces superoxide production by neutrophils.
abstract: OBJECTIVE
  Neutrophils when activated generate a respiratory burst which has been implicated in the pathogenesis of primary systemic vasculitis. Neutrophils from patients with vasculitis have a greater respiratory burst than normal healthy donors. The aim of this study was to assess the effects of antioxidant treatment (vitamins E and C) on the generation of a respiratory burst from neutrophils isolated from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis.
  
  
  METHODS
  Neutrophils were isolated from patients with systemic vasculitis and healthy donors. Spontaneous superoxide generation was measured by the reduction of ferricytochrome c. The patients were treated with antioxidants, vitamins E and C, and spontaneous superoxide generation, vitamin C and total antioxidant capacity were measured before and after treatment.
  
  
  RESULTS
  The treatment of the patients with antioxidants resulted in a reduction in spontaneous superoxide generation (pre-treatment 8.41+/-0.7 nmol/10(6) cells; post-treatment 5.64+/-0.6 nmol/10(6) cells; P<0.05). There was no significant difference in the superoxide generation from normal controls who did not receive treatment, measured prior to commencement of the study and 10 days later (first reading 4.81+/-0.5 nmol/10(6) cells; second reading 5.32+/-0.4 nmol/10(6) cells; P>0.05). Total antioxidant capacity increased significantly following treatment with vitamins C and E (555.4+/-142 vs. 668.6+/-186 micromol/l trolox equivalent; P=0.01) as did vitamin C concentrations (56.5+/-27 vs. 137.7+/-64 micromol/l; P=0.002).
  
  
  CONCLUSIONS
  In this preliminary study, the treatment of patients with antioxidants, vitamins E and C, reduced neutrophil generation of superoxide and suggests that antioxidants may have an important role as adjuvant therapy. The evidence presented should form the basis of a larger randomized placebo-controlled trial of vitamins E and C as adjuvant therapy in patients with ANCA-associated systemic vasculitis.
authors.affiliation: MRC Centre for Immune Regulation, Department of Medicine, The Medical School, Birmingham University, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: L
authors.initials: L
authors.lastname: Harper
authors.forename: S L
authors.initials: SL
authors.lastname: Nuttall
authors.forename: U
authors.initials: U
authors.lastname: Martin
authors.forename: C O S
authors.initials: CO
authors.lastname: Savage
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism*; D014810:Vitamin E / Q000627:therapeutic use*
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D000975:Antioxidants; D013481:Superoxides; D014810:Vitamin E; D001205:Ascorbic Acid