title: N-acetyl-cysteine accelerates transfer of diabetes into non-obese diabetic scid mice.
abstract: OBJECTIVE
  Type 1 diabetes mellitus is caused by autoimmune pancreatic beta cell destruction, and the destructive process involves several molecular mechanisms including oxygen-reactive species. A cysteine derivative, N-acetyl-cysteine, is widely used as an antioxidant, but the role of N-acetyl-cysteine in the protection of pancreatic beta cells in type 1 diabetes remains unclear. The aim of this study was to clarify the effect of N-acetyl-cysteine on beta cells using an adoptive transfer system in a murine model of type 1 diabetes.
  
  
  METHODS
  Splenocytes from diabetic female non-obese diabetic mice were transferred into female non-obese diabetic scid/ scid recipients to induce diabetes. Just after transfer, N-acetyl-cysteine was administered to non-obese diabetic scid recipients. Two weeks after transfer, the pancreas of the recipients was examined histologically, and cytokine mRNA expression in the pancreas was analysed. In vitro, CD4-positive splenocytes from diabetic donor mice were stimulated with anti-CD3 and anti-CD28 antibodies with or without N-acetyl-cysteine.
  
  
  RESULTS
  Treatment with N-acetyl-cysteine significantly accelerated the transfer of diabetes into non-obese diabetic scid recipients. Treatment with N-acetyl-cysteine accelerated the infiltration of mononuclear cells accompanied by CD8-positive cells into the intra-islet region of the recipient's pancreas, and enhanced interferon-gamma mRNA expression in the pancreas. In vitro, treatment with N-acetyl-cysteine enhanced interferon-gamma and interleukin-2 production by CD4-positive splenocytes of the diabetic donor mice.
  
  
  CONCLUSIONS
  N-acetyl-cysteine accelerates the transfer of diabetes into non-obese diabetic scid mice and this effect is accompanied by the promotion of local infiltration and T-helper cell type 1 responses.
authors.affiliation: Keio University School of Medicine, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Irie
authors.forename: A
authors.initials: A
authors.lastname: Shimada
authors.forename: Y
authors.initials: Y
authors.lastname: Oikawa
authors.forename: T
authors.initials: T
authors.lastname: Shigihara
authors.forename: T
authors.initials: T
authors.lastname: Saruta
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D017710:Lymphocyte Transfusion; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D016133:Polymerase Chain Reaction; D013154:Spleen; D013997:Time Factors
chemical_list: D016207:Cytokines; D000111:Acetylcysteine