IMMUNOHISTOCHEMICAL DETECTION OF TUMOR-NECROSIS-FACTOR-ALPHA, OTHER CYTOKINES AND ADHESION MOLECULES IN HUMAN LIVERS WITH ALCOHOLIC HEPATITIS

This immunohistochemical study was designed to investigate the possibl e contribution to and topographical distribution of some important cyt okines, such as tumour necrosis factor alpha (TNFalpha) and interleuki ns, in acute alcoholic hepatitis. The well-known inductive capacity of these cytokines with respect to the expression and/or up-regulation o f adhesion molecules, such as intercellular adhesion molecule-1 (ICAM- 1) and endothelial leukocyte adhesion molecule-1 (ELAM-1), was a furth er point to be studied. Moreover, the proposed induction of adhesion m olecules might also be associated with the activation and attraction o f a special population of inflammatory cells characteristic for alcoho lic hepatitis. Frozen liver samples from patients who died with signs of acute alcoholic hepatitis were evaluated using the alkaline phospha tase anti-alkaline phosphatase immunostaining technique and also singl e and double indirect immunofluorescence. In acute alcoholic hepatitis TNFalpha could be detected predominantly in ballooned hepatocytes, wh ich often contained alcoholic hyalin (Mallory bodies). Moreover, TNFal pha showed a co-distribution with ICAM-1 expressed in the membranes of hepatocytes and with the occurrence of CD11b positive polymorphonucle ar leukocytes (neutrophils) suggesting a possible major role of the be ta2-integrin Mac-1 as a ligand for ICAM-1. No induction of ELAM-1 coul d be found. In alcoholic hepatitis cytokines may be responsible for th e induction of the adhesion molecule ICAM-1 on hepatocytic membranes a nd activate a defined population of inflammatory cells, thus contribut ing to the characteristic histological picture of acute alcoholic hepa titis with its concentration of neutrophils especially in areas with b allooned Mallory body-containing hepatocytes. Our results are in line with clinical findings showing high levels of TNFalpha and interleukin -1 in sera of patients with alcoholic hepatitis and with the already r eported expression of ICAM-1 on hepatocytes.