In the USA the number of chronic alcoholics is estimated to be between 9 and 10 million. In large metropolitan areas, cirrhosis of the liver is the fourth most common causes of death in the usually most productive years of our lives, between the ages of 35 and 54. Alcoholic hepatitis, a curable stage of liver injury, generally precedes the development of cirrhosis. Currently and understanding of the mechanism(s) involved in the transition of alcoholic hepatitis into cirrhosis or perpetuation of the disease even when the patients stop alcohol consumption, remains a mystery. The participation and role of the immune system in the progression of the disease is an area of interest which needs clarification. This project is in response to a special announcement for Research Grants on Alcohol and Immunology.
The specific aims of this research proposal are:1) to determine in alcoholic liver injury the lymphocyte subsets that participate in the immune response of the hepatocytes, and 2) to test for the presence of the interleukins and for the expression of the major histocompatibility complex molecules on the liver. All of these elements seem to be necessary to induce and perpetuate liver cell injury and death. In order to achieve the aims of this project, monoclonal antibodies will be used to demonstrate the various antigens in needle liver biopsies of alcoholic patients by the indirect double immunoperoxidase technique. Our preliminary data indicates that helper (CD-4 and cytolytic (CD-8 lymphocytes are present in a predictable fashion in the alcoholic liver. Furthermore the histocompatibility antigen, class I molecules, are expressed on the membrane of the liver cells and alcohol increases them, a feature that suggests that they may be involved in the development and progression of alcoholic injury. The presence in the liver of the key mediators of the immune response would argue in favor their participation in eliciting the injury to the hepatocytes, that is the hallmark of alcoholic liver disease. The long-term goal of this research is to provide an explanation for the mechanism(s) of alcohol-induced liver injury that may be of help to investigators in the future by serving as a baseline to develop new forms of treatment or preventive measures in order to stop damage and progression of the disease.
