Immunolocalization of alpha interferon in liver disease.

Abstract

SUMMARY The expression ofimmunoreactive a interferon was examined in 78 liver biopsy specimens using an indirect immunoperoxidase technique. Biopsy specimens included cases of acute viral hepatitis, chronic active hepatitis, primary biliary cirrhosis, alcoholic hepatitis, large bile duct obstruction and normal liver. Kupffer cells were positive for a interferon in all cases. Hepatocytes were negative for a interferon in normal liver but in acute viral hepatitis were positive in perivenular and necrotic areas. Hepatocytes were positive in periportal areas, associated with piecemeal necrosis, in chronic active hepatitis and primary biliary cirrhosis, and were positive in perivenular areas in alcoholic hepatitis and large bile duct obstruction.The unexpected finding of a interferon in hepatocytes in non-viral liver disease indicates that the presence of this substance in liver cells cannot be taken as a specific marker of viral infection.Hepatitis B (HBV) virus is not directly cytopathic and T cell mediated cytolysis is considered to be the means of viral elimination in HBV infection. The recognition of infected cells by cytotoxic T lymphocytes depends on the association between viral determinants and class I major histocompatibility complex (MHC) molecules. The interferons are known to induce an increase of synthesis and display of MHC class I molecules, and it has been proposed that during acute HBV infection, interferon promotes hepatocyte MHC class I display, which increases the possibility of immune attack by cytotoxic T cells. There is indirect evidence to support this hypothesis. In uncomplicated acute HBV infection plasma interferon concentrations rise,' and increased hepatocyte expression of (2 microglobulin (a subunit of HLA class I antigen) has been shown.2 Recently a technique for the detection of immunoreactive a interferon (IFN-a) in formalin fixed, paraffin wax embedded tissue has been developed.3 We used this technique on a series of liver biopsy specimens to investigate the expression of a interferon in viral hepatitis and in other liver diseases to ascertain ifits expression by hepatocytes is a specific indicator of viral infection. Material and methodsSeventy eight percutaneous and wedge liver biopsy specimens from nine cases of acute viral hepatitis, 14

Enhanced expression of type I interferon and toll-like receptor-3 in primary biliary cirrhosis

“…36,[38][39][40] Our immunohistochemical analyses showed that TLR-3 and IFN-b localize primarily to portal tract macrophages and hepatocytes, whereas IFN-a was detected primarily in inflammatory cells (plasma cells, lymphocytes, macrophages) in the portal tract and in Kupffer cells. These data are consistent with previous studies of IFN-a localization in liver biopsies from patients with viral hepatitis, [41][42][43][44][45][46] in which Kupffer cells, lymphocytes and macrophages showed IFN-a positive staining. While hepatocytes have also been previously reported to express IFNa 41,[43][44][45] in chronic viral hepatitis, the expression of IFN-b in hepatocytes has not been demonstrated by Type I interferon in primary biliary cirrhosis Y Takii et al immunohistochemistry in vivo.…”

“…These data are consistent with previous studies of IFN-a localization in liver biopsies from patients with viral hepatitis, [41][42][43][44][45][46] in which Kupffer cells, lymphocytes and macrophages showed IFN-a positive staining. While hepatocytes have also been previously reported to express IFNa 41,[43][44][45] in chronic viral hepatitis, the expression of IFN-b in hepatocytes has not been demonstrated by Type I interferon in primary biliary cirrhosis Y Takii et al immunohistochemistry in vivo. Only a few report is available concerning the mRNA expression of IFN-b in hepatocytes in vivo or hepatocyte cell lines in vitro.…”

Lymphocyte subsets and β2-microglobulin expression in chronic hepatitis C/non-A, non-B. Effects of interferon-alpha treatment

“…Also in hepalitis \i a possible correlation between HLA class I aniigen display on hepatocytes and hepatic inflammatory activity has been demonstrated [8, 13.16.17]. The strong /^-MG expression, especially in CAH, may be indueed by locally produced endogenous IFN and correlates with ihc finding of IFN-y and IFN-a in intrahcpatie mononuclear cells [19] and of IFN-a in hepaLocytes [24] in patients with chronic hepatitis. Due to increased cell turnover and shedding, scrum-/^-MG levels will also increase, although serum levels oflFN are hardly delectable |25], 11 this hypothesis is correct the hepatocyte fi^-MG expression is secondary to hepatic inflammation.…”

Effects of cytokines on the liver

“…Anemia leads to the synthesis of erythropoietin in the liver (161). IFN-a is produced in hepatocytes both in viral hepatitis and nonviral liver diseases (162).…”