title: Opposite effects of low and high dose supplementation of vitamin E on survival of MRL/lpr mice.
abstract: OBJECTIVE
  The purpose of this study is to investigate the effects of vitamin E supplementation on the autoimmune disease course in MRL/lymphoproliferative mice.
  
  
  METHODS
  Three-month-old MRL/lymphoproliferative lpr female mice were fed an AIN-76 diet containing 50 mg/kg (control), 250 mg/kg (E5), 375 mg/kg (E7.5), or 500 mg/kg (E10) all-rac-alpha-tocopheryl acetate. Eight mice per group were killed for analysis after two months of experimental diets, and the rest of the mice were followed up to observe their proteinuria levels and life span.
  
  
  RESULTS
  The data suggest that the life span of the E5 group was longer than the E10 group. Though alpha-tocopherol content in the plasma, liver, and kidneys increased in the mice fed the diet supplemented with vitamin E, the thiobarbituric acid reactive substance values in the liver and kidneys among these groups were not significantly different. IgM anti-ds-DNA and anticardiolipin antibodies were significantly higher in the E10 group than in those of the other groups. Phytohemagglutinin-stimulated interleukin (IL)-2 secretion was significantly lower, but concanavalinA-stimulated IL-4 and IL-10 production was significantly higher in the E10 group compared with the control group. The in vitro study also showed decreased IL-2 secretion and messenger RNA expression in phytohemagglutinin-stimulated splenocytes cultured in medium supplemented with high doses of vitamin E, but increased IL-2 with low doses of vitamin E.
  
  
  CONCLUSIONS
  Our data suggest that low and high dose supplementation of vitamin E has the opposite effect on the survival of MRL/lpr mice. The inhibitory effect of Th1 from high vitamin E content may not be beneficial for those suffering from Th2 prone autoimmune diseases, such as systemic lupus erythematosus.
authors.affiliation: Department of Biochemical Science and Technology, Institute of Microbiology and Biochemistry, College of Life Science, National Taiwan University, Taipei, Taiwan, Republic of China.
authors.forename: Chia-Chien
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Bi-Fong
authors.initials: BF
authors.lastname: Lin
mesh_terms: D000818:Animals; D000975:Antioxidants; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005260:Female; D007376:Interleukin-2 / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011507:Proteinuria; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D024505:Tocopherols; D014810:Vitamin E / Q000008:administration & dosage*; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000975:Antioxidants; D007376:Interleukin-2; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D024502:alpha-Tocopherol; D024505:Tocopherols