Experimental Studies on the Relationship Between Immune Responses and Liver Damage Induced by Ethanol After Immunization With Homologous Acetaldehyde Adducts

Abstract

Background It has been considered that acetaldehyde (AcH) adducts induce liver injury through an immune response. Previous experimental studies showed that hepatic necrosis, inflammatory cell infiltration, and hepatic fibrosis were induced in guinea pigs immunized with heterologous human AcH adducts and ethanol feeding. AcH modification of foreign protein may markedly increase immunogenicity of the protein itself, leading to enhanced formation of immune complex and possible liver injury. The present study investigated whether immune responses and alcoholic liver disease would be induced in mice by immunization with mouse albumin‐AcH adducts and ethanol feeding.Methods 6B6 mice were divided into six groups with or without immunization and ethanol feeding. Mice were immunized with mouse albumin‐AcH adducts three times at 2‐week intervals and fed ethanol for 10 weeks. The stimulation index of [3H]thymidine uptake into lymphocytes cultured with mouse albumin or mouse albumin‐AcH adducts was measured. Histologic findings of the liver were examined, and the plasma levels of aspartate transaminase and alanine aminotransferase were also measured.Results The stimulation index was increased remarkably in ethanol‐fed mice that were immunized with mouse albumin‐AcH adducts. However, neither inflammatory cell infiltration nor hepatic necrosis was observed in the liver. There were also no differences in the plasma activities of aspartate transaminase and alanine aminotransferase between the group of mice regardless of ethanol feeding or immunization.Conclusion Although marked immune responses were observed, no liver damage was induced by long‐term ethanol feeding in our mouse model using AcH‐homologous albumin adducts. These results suggest that homologous protein adducts may not induce liver injury by long‐term ethanol feeding or may have lower immunogenicity than heterologous protein adducts. These results also suggest that nonreduced AcH adducts and/or a larger amount of ethanol may be needed for liver injury in this model.