Induction of tumor necrosis factor α production by human hepatocytes in chronic viral hepatitis

• Published in: The Journal of experimental medicine Vol. 179; no. 3; pp. 841 - 848
• Main Authors: GONZALEZ-AMARO, R, GARCIA-MONZON, C, GARCIA-BUEY, L, MORENO-OTERO, R, ALONSO, J. L, YAGÜE, E, PIVEL, J. P, LOPEZ-CABRERA, M, FERNANDEZ-RUIZ, E, SANCHEZ-MADRID, F
• Format: Journal Article
• Language: English
• Published: New York, NY Rockefeller University Press 01.03.1994; The Rockefeller University Press
• Subjects: Antibodies, Monoclonal; Biological and medical sciences; Cell Line; Epitopes - analysis; Hepatitis B - metabolism; Hepatitis B - pathology; Hepatitis C - metabolism; Hepatitis C - pathology; Hepatoblastoma - metabolism; Human viral diseases; Humans; Immunohistochemistry; Infectious diseases; Kupffer Cells - cytology; Kupffer Cells - metabolism; Kupffer Cells - pathology; Liver - cytology; Liver - metabolism; Liver - pathology; Liver Cirrhosis, Alcoholic - metabolism; Liver Cirrhosis, Alcoholic - pathology; Liver Neoplasms - metabolism; Medical sciences; RNA, Messenger - analysis; RNA, Messenger - metabolism; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - analysis; Tumor Necrosis Factor-alpha - biosynthesis; Viral diseases; Viral hepatitis; Infection; Human; Chronic; Viral hepatitis; Messenger RNA; Hepatocyte; Viral disease; Cytokine; Digestive diseases; Hepatic disease; Biosynthesis; Tumor necrosis factor α
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.179.3.841

Tumor necrosis factor alpha (TNF-alpha) is a multifunctional cytokine that has an important role in the pathogenesis of inflammation, cachexia, and septic shock. Although TNF-alpha is mainly produced by macrophages, there is evidence regarding TNF-alpha production by cells that are not derived from bone marrow. TNF-alpha production by normal and inflamed human liver was assessed at both mRNA and protein levels. Using a wide panel of novel anti-TNF-alpha monoclonal antibodies and a specific polyclonal antiserum, TNF-alpha immunoreactivity was found in hepatocytes from patients chronically infected with either hepatitis B virus (HBV) or hepatitis C virus. Minimal TNF-alpha immunoreactivity was detected in the mononuclear cell infiltrate and Kupffer cells. In situ hybridization experiments using a TNF-alpha RNA probe showed a significant expression of TNF-alpha mRNA in hepatocytes, Kupffer cells, and some infiltrating mononuclear cells. By contrast, TNF-alpha was detected at low levels in liver biopsies from normal individuals or patients with alcoholic liver disease and low expression of TNF-alpha mRNA was observed in these specimens. Transfection of HepG2 hepatoblastoma cells with either HBV genome or HBV X gene resulted in induction of TNF-alpha expression. Our results demonstrate that viral infection induces, both in vivo and in vitro, TNF-alpha production in hepatocytes, and indicate that the HBV X protein may regulate the expression of this cytokine. These findings suggest that TNF-alpha may have an important role in human liver diseases induced by viruses.