Animal model for severe alcoholic hepatitis by chronic ethanol feeding and immunization with fusions of dendritic cells and acetaldehyde adducts.

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(1) Mouse albumin-acetalciehyde adduct (ADT) was prepared with the reducing agent according to the method of Israel et al (Proc Nati Acad Sci USA 83 : 7923,1986).(2) In order to choose the mouse that responds to ADT well, four species of mice (B10S, BALB/C, C3H, and B6 mouse) with different strains were prepared. Mice were immunized with ADT. The lymphocytes were obtained from the systemic lymph node of each mouse, and in vitro lymphocyte stimulation test was performed. The stimulation index was remarkably higher in B6 mice than in any other mice.(3) B6 mice were divided into 6 groups with or without immunization and ethanol feeding (10 weeks). The stimulation index of ^3H-thymidine uptake into lymphocytes cultured with mouse albumin or ADT was measured, The stimulation .index was increased remarkably in ethanol-fed mice immunized with ADT. However, no elevation in plasma AST and ALT levels was observed.,and neither inflammatory cell infiltration nor hepatic necrosis was observed in the liver.(4) As immune response was induced in the lymphocyte in this model, we are trying to isolate T cells from the lymphnode, and inject T cells into portal or systemic vein to investigate the induction of immune response and liver damage. We also made fusions of dendritic cells and ADT. We are trying to make a model for alcoholic hepatitis by chronic ethanol feeding and immunization with this fusion cells.