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. 1990 Apr;43(4):298–302. doi: 10.1136/jcp.43.4.298

Immunohistochemical studies of intrahepatic tumour necrosis factor alpha in chronic liver disease.

K Yoshioka 1, S Kakumu 1, M Arao 1, Y Tsutsumi 1, M Inoue 1, T Wakita 1, T Ishikawa 1, M Mizokami 1
PMCID: PMC502358  PMID: 1692847

Abstract

To determine the intrahepatic production of tumour necrosis factor alpha (TNF alpha) in chronic liver disease three monoclonal antibodies were used against TNF alpha in immunohistochemical studies of liver tissue sections from patients with chronic liver disease. All three monoclonal antibodies stained infiltrating mononuclear cells. Monoclonal antibody II 7C2 also stained the cytoplasm or nucleus, or both, of a varied number of hepatocytes from nine patients with chronic hepatitis B virus infection, suggesting that the antigenic epitope related to hepatitis B core antigen (HBcAg) crossreacted with II7C2. The other two monoclonal antibodies, III2F3 and IV3E5, stained significantly larger numbers of mononuclear cells in cases of chronic active hepatitis B than in chronic persistent hepatitis B, or hepatitis B related liver cirrhosis. III2F3 stained significantly larger numbers of mononuclear cells in non-A, non-B chronic active hepatitis than in chronic persistent hepatitis B or hepatitis B related liver cirrhosis. These results indicate that TNF alpha is produced and secreted by infiltrating mononuclear cells in focal inflammatory areas of the liver, and suggest that TNF alpha may have a role in the inflammatory activity of chronic liver disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  2. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Collins T., Lapierre L. A., Fiers W., Strominger J. L., Pober J. S. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci U S A. 1986 Jan;83(2):446–450. doi: 10.1073/pnas.83.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Creasey A. A., Doyle L. V., Reynolds M. T., Jung T., Lin L. S., Vitt C. R. Biological effects of recombinant human tumor necrosis factor and its novel muteins on tumor and normal cell lines. Cancer Res. 1987 Jan 1;47(1):145–149. [PubMed] [Google Scholar]
  5. Darlington G. J., Wilson D. R., Lachman L. B. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J Cell Biol. 1986 Sep;103(3):787–793. doi: 10.1083/jcb.103.3.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dudley F. J., Fox R. A., Sherlock S. Cellular immunity and hepatitis-associated, Australia antigen liver disease. Lancet. 1972 Apr 1;1(7753):723–726. doi: 10.1016/s0140-6736(72)90234-6. [DOI] [PubMed] [Google Scholar]
  8. Eddleston A. L., Williams R. Inadequate antibody response to hBAg or suppressor T-cell defect in development of active chronic hepatitis. Lancet. 1974 Dec 28;2(7896):1543–1545. doi: 10.1016/s0140-6736(74)90287-6. [DOI] [PubMed] [Google Scholar]
  9. Fuji A., Kakumu S., Ohtani Y., Murase K., Hirofuji H., Tahara H. Interferon-gamma production by peripheral blood mononuclear cells of patients with chronic liver disease. Hepatology. 1987 May-Jun;7(3):577–581. doi: 10.1002/hep.1840070327. [DOI] [PubMed] [Google Scholar]
  10. Jelinek D. F., Lipsky P. E. Enhancement of human B cell proliferation and differentiation by tumor necrosis factor-alpha and interleukin 1. J Immunol. 1987 Nov 1;139(9):2970–2976. [PubMed] [Google Scholar]
  11. Kakumu S., Arao M., Yoshioka K., Tsutsumi Y., Inoue M. Distribution of HBcAg in hepatitis B detected by immunoperoxidase staining with three different preparations of anti-HBc antibodies. J Clin Pathol. 1989 Mar;42(3):284–288. doi: 10.1136/jcp.42.3.284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kato Y., Nakagawa H., Kobayashi K., Hattori N., Hatano K. Interferon production by peripheral lymphocytes in HBsAg-positive liver diseases. Hepatology. 1982 Nov-Dec;2(6):789–790. doi: 10.1002/hep.1840020607. [DOI] [PubMed] [Google Scholar]
  13. Magilavy D. B., Rothstein J. L. Spontaneous production of tumor necrosis factor alpha by Kupffer cells of MRL/lpr mice. J Exp Med. 1988 Aug 1;168(2):789–794. doi: 10.1084/jem.168.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  15. Nawroth P. P., Bank I., Handley D., Cassimeris J., Chess L., Stern D. Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1363–1375. doi: 10.1084/jem.163.6.1363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ostensen M. E., Thiele D. L., Lipsky P. E. Tumor necrosis factor-alpha enhances cytolytic activity of human natural killer cells. J Immunol. 1987 Jun 15;138(12):4185–4191. [PubMed] [Google Scholar]
  17. Scheurich P., Thoma B., Ucer U., Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987 Mar 15;138(6):1786–1790. [PubMed] [Google Scholar]
  18. Shalaby M. R., Aggarwal B. B., Rinderknecht E., Svedersky L. P., Finkle B. S., Palladino M. A., Jr Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors. J Immunol. 1985 Sep;135(3):2069–2073. [PubMed] [Google Scholar]
  19. Steffen M., Ottmann O. G., Moore M. A. Simultaneous production of tumor necrosis factor-alpha and lymphotoxin by normal T cells after induction with IL-2 and anti-T3. J Immunol. 1988 Apr 15;140(8):2621–2624. [PubMed] [Google Scholar]
  20. Takahashi K., Machida A., Funatsu G., Nomura M., Usuda S., Aoyagi S., Tachibana K., Miyamoto H., Imai M., Nakamura T. Immunochemical structure of hepatitis B e antigen in the serum. J Immunol. 1983 Jun;130(6):2903–2907. [PubMed] [Google Scholar]
  21. Wright S. C., Bonavida B. Studies on the mechanism of natural killer cell-mediated cytotoxicity. VII. functional comparison of human natural killer cytotoxic factors with recombinant lymphotoxin and tumor necrosis factor. J Immunol. 1987 Mar 15;138(6):1791–1798. [PubMed] [Google Scholar]
  22. Yamazaki S., Onishi E., Enami K., Natori K., Kohase M., Sakamoto H., Tanouchi M., Hayashi H. Proposal of standardized methods and reference for assaying recombinant human tumor necrosis factor. Jpn J Med Sci Biol. 1986 Jun;39(3):105–118. doi: 10.7883/yoken1952.39.105. [DOI] [PubMed] [Google Scholar]
  23. Yokota S., Geppert T. D., Lipsky P. E. Enhancement of antigen- and mitogen-induced human T lymphocyte proliferation by tumor necrosis factor-alpha. J Immunol. 1988 Jan 15;140(2):531–536. [PubMed] [Google Scholar]
  24. Yoshioka K., Kakumu S., Arao M., Tsutsumi Y., Inoue M. Tumor necrosis factor alpha production by peripheral blood mononuclear cells of patients with chronic liver disease. Hepatology. 1989 Nov;10(5):769–773. doi: 10.1002/hep.1840100504. [DOI] [PubMed] [Google Scholar]

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