title: Alcohol facilitates CD1d loading, subsequent activation of NKT cells, and reduces the incidence of diabetes in NOD mice.
abstract: BACKGROUND
  Ethanol ('alcohol') is a partly hydrophobic detergent that may affect the accessibility of glycolipids thereby influencing immunological effects of these molecules.
  
  
  METHODS
  The study included cellular in vitro tests using α-galactosylceramide (αGalCer), and in vivo NOD mice experiments detecting diabetes incidence and performing behavioural and bacterial analyses.
  
  
  RESULTS
  Alcohol in concentrations from 0.6% to 2.5% increased IL-2 production from NKT cells stimulated with αGalCer by 60% (p<0.05). CD1d expressed on HeLa cells contained significantly increasing amounts of αGalCer with increasing concentrations of alcohol, suggesting that alcohol facilitated the passive loading of αGalCer to CD1d. NOD mice were found to tolerate 5% ethanol in their drinking water without signs of impairment in liver function. Giving this treatment, the diabetes incidence declined significantly. Higher numbers of CD3+CD49b+ NKT cells were found in spleen and liver of the alcohol treated compared to the control mice (p<0.05), whereas the amount of CD4+Foxp3+ regulator T cells did not differ. Increased concentrations of IFN-γ were detected in 24-hour blood samples of alcohol treated mice. Behavioural studies showed no change in attitude of the ethanol-consuming mice, and bacterial composition of caecum samples was not affected by alcohol, disqualifying these as protective mechanisms.
  
  
  CONCLUSIONS
  Alcohol facilitates the uptake of glycolipids and the stimulation of NKT cells, which are known to counteract Type 1 diabetes development. We propose that this is the acting mechanism by which treatment with alcohol reduces the incidence of diabetes in NOD mice. This is corroborated by epidemiology showing beneficial effect of alcohol to reduce the severity of atherosclerosis and related diseases.
authors.affiliation: Bartholin Instituttet, Rigshospitalet, Copenhagen, Denmark. buschard@dadlnet.dk
authors.forename: Karsten
authors.initials: K
authors.lastname: Buschard
authors.forename: Axel Kornerup
authors.initials: AK
authors.lastname: Hansen
authors.forename: Karen
authors.initials: K
authors.lastname: Jensen
authors.forename: Dicky J
authors.initials: DJ
authors.lastname: Lindenbergh-Kortleve
authors.forename: Lilian F
authors.initials: LF
authors.lastname: de Ruiter
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Krohn
authors.forename: Majbritt R
authors.initials: MR
authors.lastname: Hufeldt
authors.forename: Finn K
authors.initials: FK
authors.lastname: Vogensen
authors.forename: Bent
authors.initials: B
authors.lastname: Aasted
authors.forename: Thomas
authors.initials: T
authors.lastname: Osterbye
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.forename: Edward E
authors.initials: EE
authors.lastname: Nieuwenhuis
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D058645:Denaturing Gradient Gel Electrophoresis; D003920:Diabetes Mellitus / Q000276:immunology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D055611:Natural Killer T-Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D055610:Antigens, CD1d; D000431:Ethanol