title: Intrahepatic MxA expression is correlated with interferon-alpha expression in chronic and fulminant hepatitis.
abstract: Interferon-alpha (IFN-alpha) has potent pro-inflammatory and anti-viral functions. It exerts its effects by inducing intracellular proteins such as MxA. To analyse the role of intrahepatic interferon activation, IFN-alpha and MxA expression was studied by immunohistochemistry in explant livers of 20 patients with fulminant hepatic failure (FHF), 41 patients with chronic liver disease (CLD), and ten normal controls (NCs). In NCs only small numbers of Kupffer cells, but no hepatocytes, showed IFN-alpha and MxA expression. In contrast, significantly enhanced numbers of IFN-alpha- and MxA-positive Kupffer cells, along with small numbers of MxA-positive and larger numbers of IFN-alpha-positive lymphocytes, were found in CLD and in FHF. MxA protein was also expressed on hepatocytes and bile ducts in the vicinity of IFN-alpha-positive inflammatory infiltrates (hepatocytes: NCs: 0%, CLD: 8%, FHF: 68%; bile ducts: NCs: 19%, CLD: 46%, FHF: 83%). A significant correlation was found between the numbers of IFN-alpha- and MxA-positive cells (r=0.67, p<0.001). Thus, large amounts of IFN-alpha are released in the livers of patients with FHF, which is likely to contribute to immune-mediated liver cell damage. Intrahepatic MxA expression corresponds to IFN-alpha produced particularly by infiltrating inflammatory cells, rather than by hepatocytes themselves.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Sigmund Freud Strasse 25, D-53105 Bonn, Germany. l.leifeld@uni-bonn.de
authors.forename: L
authors.initials: L
authors.lastname: Leifeld
authors.forename: J
authors.initials: J
authors.lastname: Ramakers
authors.forename: A M
authors.initials: AM
authors.lastname: Schneiders
authors.forename: F L
authors.initials: FL
authors.lastname: Dumoulin
authors.forename: M
authors.initials: M
authors.lastname: Sterneck
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: T
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: U
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000998:Antiviral Agents / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism; D019204:GTP-Binding Proteins; D006521:Hepatitis, Chronic / Q000378:metabolism; D006525:Hepatitis, Viral, Human / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D016898:Interferon-alpha / Q000378:metabolism*; D017093:Liver Failure / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D064547:Myxovirus Resistance Proteins; D011506:Proteins / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D011506:Proteins; D019204:GTP-Binding Proteins