title: Vitamin E uncouples joint destruction and clinical inflammation in a transgenic mouse model of rheumatoid arthritis.
abstract: OBJECTIVE
  Reactive oxygen species are thought to play a role in rheumatoid arthritis (RA) in humans. We postulated that antioxidant treatment could have a beneficial effect in this disease. We therefore investigated the effects of vitamin E in the transgenic KRN/NOD mouse model of RA.
  
  
  METHODS
  Mice were treated by gavage with oral vitamin E (alpha-tocopherol). Clinical, histologic, and biochemical parameters were assessed for 6 weeks.
  
  
  RESULTS
  Vitamin E treatment did not modify the clinical features of the disease (date of onset or disease intensity, as measured by the articular index), but it did prevent joint destruction, as measured by qualitative and semiquantitative analyses. Redox status did not differ between treated and control mice. White blood cell chemiluminescence was higher in transgenic KRN/NOD mice than in controls, but vitamin E treatment attenuated this difference. Vitamin E treatment of the transgenic animals led to a significant decrease in the levels of interleukin-(IL-1beta) but not tumor necrosis factor alpha.
  
  
  CONCLUSIONS
  Vitamin E seems to uncouple joint inflammation and joint destruction in this model of RA, with a beneficial effect on joint destruction. Since many investigations are currently in progress to evaluate the benefit of interventions targeted toward anti-IL-1beta, our findings suggest opportunities of therapeutic interest in human RA.
authors.affiliation: INSERM U479, Faculté Xavier Bichat, and Centre Hospitalo-Universitaire Xavier Bichat, 46 rue Henri Huchard, Paris 75018, France. frbandt@bichat.inserm.fr
authors.forename: Michel
authors.initials: M
authors.lastname: De Bandt
authors.forename: Maggy
authors.initials: M
authors.lastname: Grossin
authors.forename: Fathi
authors.initials: F
authors.lastname: Driss
authors.forename: Joël
authors.initials: J
authors.lastname: Pincemail
authors.forename: Catherine
authors.initials: C
authors.lastname: Babin-Chevaye
authors.forename: Catherine
authors.initials: C
authors.lastname: Pasquier
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D001835:Body Weight; D004195:Disease Models, Animal; D005978:Glutathione / Q000097:blood; D006861:Hydrogen Peroxide / Q000097:blood; D007375:Interleukin-1 / Q000097:blood; D028421:Isoprostanes / Q000652:urine; D007596:Joints / Q000276:immunology / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008163:Luminescent Measurements; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014810:Vitamin E / Q000097:blood / Q000494:pharmacology*; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D007375:Interleukin-1; D028421:Isoprostanes; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D015054:Zymosan; D006861:Hydrogen Peroxide; D005978:Glutathione