Immunologic reactivity and alcoholic liver disease

Investigation of cell mediated immunologic reactivity by means of lymphocyte transformation and production of migration inhibition factor (MIF) improves the diagnostic and therapeutic perspective in the alcoholic with liver disease. Malnourished alcoholics with liver disease frequently exhibit reduced lymphocyte reactivity to the mitogen PHA; this is attributable to a reversible decrease in the synthetic capacity of DNA which occurs as a result of liver injury, nutritional deficiency, or circulating antagonists. Immunologic hyperreactivity to alcoholic hyaline may be of crucial importance in the transformation of alcoholic hepatitis to cirrhosis. Despite a decrease in the total number of T cells and reduced responsivenss to PHA, alcoholic hyaline evokes an increase in MIF. Supernatants of sensitized lymphocytes stimulated with this material produce an increase in the incorporation of proline into collagen. This actin like protein may serve as a neoantigen and may stimulate antibody forming cells or T lymphocytes to release biologically active products. Immunologic competence, as reflected in lymphocyte response to PHA, increases in the alcoholic with the improvement of hepatic reserve induced by abstinence and correction of nutritional deficiencies. Immunologic hyperactivity with release of migration inhibition factor and fibrogenic factor persists despite progressive deterioration of the liver and eventually leads to a vicious cycle. Drugs which suppress immunologic response and reduce fibrogenesis may be valuable therapeutic adjuncts in selected alcoholics with progressive hepatic cell destruction despite abstinence from alcohol and a good diet.