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Immunohistochemical detection of tumor necrosis factor-alpha, other cytokines and adhesion molecules in human livers with alcoholic hepatitis


, : Immunohistochemical detection of tumor necrosis factor-alpha, other cytokines and adhesion molecules in human livers with alcoholic hepatitis. Virchows Archiv A Pathological Anatomy & Histopathology. 423(3): 169-176

This immunohistochemical study was designed to investigate the possible contribution to and topographical distribution of some important cytokines, such as tumour necrosis factor alpha (TNF-alpha) and interleukins, in acute alcoholic hepatitis. The well-known inductive capacity of these cytokines with respect to the expression and/or up-regulation of adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1), was a further point to be studied. Moreover, the proposed induction of adhesion molecules might also be associated with the activation and attraction of a special population of inflammatory cells characteristic for alcoholic hepatitis. Frozen liver samples from patients who died with signs of acute alcoholic hepatitis were evaluated using the alkaline phosphatase anti-alkaline phosphatase immunostaining technique and also single and double indirect immunofluorescence. In acute alcoholic hepatitis TNF-alpha could be detected predominantly in ballooned hepatocytes, which often contained alcoholic hyalin (Mallory bodies). Moreover, TNF-alpha showed a co-distribution with ICAM-1 expressed in the membranes of hepatocytes and with the occurrence of CD11b positive polymorphonuclear leukocytes (neutrophils) suggesting a possible major role of the beta-2-integrin Mac-1 as a ligand for ICAM-1. No induction of ELAM-1 could be found. In alcoholic hepatitis cytokines may be responsible for the induction of the adhesion molecule ICAM-1 on hepatocytic membranes and activate a defined population of inflammatory cells, thus contributing to the characteristic histological picture of acute alcoholic hepatitis with its concentration of neutrophils especially in areas with ballooned Mallory body-containing hepatocytes. Our results are in line with clinical findings showing high levels of TNF-alpha and interleukin-1 in sera of patients with alcoholic hepatitis and with the already reported expression of ICAM-1 on hepatocytes.

US$19.90

PMID: 7694422

DOI: 10.1007/bf01614767


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