title: alpha-tocopherol supplementation decreases production of superoxide and cytokines by leukocytes ex vivo in both normolipidemic and hypertriglyceridemic individuals.
abstract: BACKGROUND
  alpha-Tocopherol plays an important role in protecting LDL against oxidation. However, additional effects of alpha-tocopherol at the intracellular level may contribute to the clinical outcome of intervention studies.
  
  
  OBJECTIVE
  We investigated whether alpha-tocopherol influences the inflammatory responses of immune cells in normolipidemic and hypertriglyceridemic subjects.
  
  
  METHODS
  RRR-alpha-Tocopherol was administered for 6 wk at a dose of 600 IU (402 mg)/d to 12 primary hypertriglyceridemic and 8 normolipidemic (fasting triacylglycerol >3.0 and <2.0 mmol/L, respectively) subjects. Cytokine production [tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-8] by mononuclear cells and superoxide production by polymorphonuclear cells and in diluted whole blood were determined before and after the intervention.
  
  
  RESULTS
  Cytokine and superoxide production did not differ significantly between hypertriglyceridemic and normolipidemic subjects. alpha-Tocopherol supplementation resulted in a 2- to 3-fold increase in the concentration of alpha-tocopherol in plasma and LDL. Whereas superoxide production in response to phorbol 12-myristate 13-acetate decreased in all subjects, response to oxidized LDL increased in 19 of 20 subjects. Response to opsonized zymosan before alpha-tocopherol supplementation was not significantly different from that after supplementation. Lipopolysaccharide-induced cytokine production by mononuclear cells decreased after supplementation with alpha-tocopherol.
  
  
  CONCLUSIONS
  alpha-Tocopherol differentially influences inflammatory responses of immune cells. These effects of alpha-tocopherol may be relevant in chronic inflammatory processes such as atherogenesis.
authors.affiliation: Department of Medicine, Division of General Internal Medicine, University Hospital Nijmegen, Nijmegen, Netherlands. b.vantis@aigazn.nl
authors.forename: L J
authors.initials: LJ
authors.lastname: van Tits
authors.forename: P N
authors.initials: PN
authors.lastname: Demacker
authors.forename: J
authors.initials: J
authors.lastname: de Graaf
authors.forename: H L
authors.initials: HL
authors.lastname: Hak-Lemmers
authors.forename: A F
authors.initials: AF
authors.lastname: Stalenhoef
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D019587:Dietary Supplements; D015536:Down-Regulation; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood*; D007962:Leukocytes / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D008055:Lipids; D008070:Lipopolysaccharides; D013481:Superoxides; D014810:Vitamin E; D013755:Tetradecanoylphorbol Acetate