Abstract
Alpha-interferon (IFN-α) has been shown to be beneficial in the treatment of chronic active hepatitis occurring as a consequence of hepatitis B virus (HBV) infection. Therefore, it has been used to reduce the high rate of allograft infection in clinical liver transplantation of HBV-positive individuals. This study was performed to evaluate the effect of IFN-α on lymphocyte subsets as well as the HLA-DR antigen expression in liver tissue. The resected livers obtained from two groups of patients who received liver transplants between 1983 and 1987 at the University of Pittsburgh were examined: group A consisted of 11 patients who were not treated (controls), and group B consisted of 10 patients (experimental group) who were treated with IFN-α for 29.4±5.6 days prior to transplantation. No differences between the two groups existed in terms of a variety of demographic and clinical characteristics. Both groups had cirrhosis as a result of chronic HBV infection. Monoclonal antibodies to cell-surface antigens unique to different lymphocyte populations and the HLA-DR antigens were used in conjunction with the avidin-biotin-immunoperoxidase technique to identify cells in tissue sections. The number of HLA-DR-positive lymphocytes in the liver was increased (P <0.005) within the portal areas in rIFN-α-treated group as compared to that seen in the untreated group (84.4±13.6/HPF vs 33.3±4.8IHPF). Moreover, the intensity of the HLA-DR antigen expression in the portal areas (P<0.02) and in the hepatic lobule (P< 0.05) was greater in the treated group than in untreated group. The number of natural killer cells was increased in the portal areas (P<0.05) of the treated group (17.2±8.2/10 HPFs vs 3.3 ±1.7/10 HPFs) as compared to the untreated group. Based upon these studies, we conclude that the use of IFN-α in the treatment of cirrhosis occurring as a result of chronic HBV infection results in: (1) an increase in the number of lymphocytes that stain for HLA-DR antigens in the portal areas; (2) a greater intensity of HLA-DR expression both in the portal and lobular areas of the liver; and (3) an increase in the number of natural killer cells present in the portal areas. These alterations in the lymphocyte and natural killer cell population, present in the liver in response to IFN-α therapy, could reflect an IFN-α-induced enhancement of the immune response to virus-infected cells.
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References
Hoofnagle JH: Therapy of chronic hepatitis B.In Hepatitis B. Gerety RJ (ed). Orlando, Academic Press, 1985, p 273
Scullard GH, Pollard RB, Smith JL, Sacks SL, Gregory PB, Robinson WS, Merigan TC: Antiviral treatment of chronic hepatitis B virus infection. I. Changes in viral markers with interferon combined with adenine arabinoside. J Infect Dis 143:772–783, 1981
Peters M, Davis GL, Dooley JS, Hoofnagle JH: The interferon system in acute and chronic hepatitis.In Progress in Liver Disease, Vol. 8. Popper H, Schaffner F (eds). Orlando, Grune & Stratton, 1986, pp 453–467
Sherlock S, Thomas HC: Treatment of chronic hepatitis due to hepatitis B virus. Lancet 2:1343–1346, 1985
Dusheiko G, Dibisceglie A, Bowyer S, Sachs E: Recombinant leukocyte interferon treatment of chronic hepatitis B. Hepatology 5:556–560, 1985
Hoofnagle JH, Smedile A, Mullen K, Peters MG, Avigan MI, Waggoner JG, Hoyer B, Gerin JL: Treatment of chronic delta hepatitis with recombinant human alpha interferon. Gastroenterology 88:1665, 1985 (abstract)
Alexander GJM, Brahm M, Fagan EA, Smith HM, Daniels HM, Eddleston ALW, Williams R: Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 2:66–69, 1987
Greenberg HB, Pollard RB, Lutwick LI, Gregory PB, Robinson WS, Merigen TC: Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med 295:517–522, 1976
Montano L, Aranguibel F, Boffill M, Goodall AH, Janossy G, Thomas HC: An analysis of the composition of the inflammatory infiltrate in autoimmune and hepatitis B virusinduced chronic liver disease. Hepatology 3:292–296, 1983
Eggink HF, Houthoff HJ, Huitema S, Gips CH, Poppema S: Cellular and humoral immune reactions in chronic active liver disease. I. Lymphocyte subsets in liver biopsies of patients with untreated idiopathic autoimmune hepatitis, chronic active hepatitis B and primary biliary cirrhosis. Clin Exp Immunol 50:17–24, 1982
Pape GR, Rieber EP, Eisenburg J, Hoffmann R, Balch CM, Paumgartner G, Riethmuller G: Involvement of the cytotoxic/suppressor T-cell subset in liver tissue injury of patients with acute and chronic liver diseases. Gastroenterology 85:657–662, 1983
Si L, Whiteside TL, Schade RR and Van Thiel DH: Studies of lymphocyte subpopulations in the liver tissue and blood of patients with chronic active hepatitis. J Clin Immunol 3:408–419, 1983
Sanchez-Tapias J, Thomas HC, and Sherlock S: Lymphocyte populations in liver biopsy specimens from patients with chronic liver disease. Gut 18:472–475, 1977
Si L, Whiteside TL, Schade RR, Starzl TE, Van Thiel DH: T-lymphocyte subsets in liver tissues of patients with primary biliary cirrhosis, patients with primary sclerosing cholangitis, and normal controls. J Clin Immunol 4:262–272, 1984
Whiteside TL, Lasky S, Si L, Van Thiel DH: Immunologic analysis of mononuclear cells in liver tissues and blood of patients with primary sclerosing cholangitis. Hepatology 5:468–474, 1985
Hirsh RL, Johnson KP: The effect of long-term administration of recombinant alpha-2 interferon on lymphocyte subsets, proliferation, and suppressor cell function in Multiple Sclerosis. J Interferon Res 6:171–177, 1986
Pignatelli M, Waters J, Brown D, Lever A, Iwarson S, Schaff Z, Gerety R, Thomas HC: HLA Class I antigens on the hepatocyte membrane during recovery from acute hepatitis B virus infection and during interferon therapy in chronic hepatitis B virus infection. Hepatology 6:349–353, 1986
Hsu A, Raine L, Fanger H: Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580, 1981
Wood GS, Wornke R: Suppression of endogenous avidin binding activity in tissues and its relevance to biotin-avidin detection systems. J Histochem Cytochem 29:1196–1204, 1981
Isaacs A, Lindenmann A: Virus interference. I. The interferons. Proc R Soc Ser B 147:258, 1957
Heron I, Hokland M, Berg K: Enhanced expression of beta 2 microglobulin and HLA antigens on human lymphoid cells by interferon. Proc Natl Acad Sci USA 75:6215–6219, 1978
Lindahl P, Leary P, Gresser I: Enhancement of the expression of histocompatibility antigens of mouse lymphoid cells by interferonin vitro. Eur J Immunol 4:779–784, 1974
Oh SH, Brandyopadhyay S, Miller DS, Starr SE: Cooperation between CD16 (LEU-11B)+ NK cells and HLA-DR+ cells in natural killing of Herpes virus-infected fibroblasts. J Immunol 139:2799–2802, 1987
Steinhoff G, Wonigeit K, Ringe B, Lauchart W, Kemnitz J, Pichlmayr R: Modified patterns of major histocompatibility complex-antigen expression in human liver grafts during rejection. Transplant Proc 19:2466–2469, 1987
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This work was supported in part by grants NIDDK 32556-05 and ACS PDT-337.
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Yoo, Y.K., Gavaler, J.S., Chen, K. et al. Alpha-interferon. Digest Dis Sci 34, 1758–1764 (1989). https://doi.org/10.1007/BF01540055
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DOI: https://doi.org/10.1007/BF01540055