Gastroenterology
Volume 118, Issue 4 , Pages 655-660 , April 2000

Interleukin 10 treatment reduces fibrosis in patients with chronic hepatitis C: A pilot trial of interferon nonresponders

  • David R. Nelson

      Affiliations

    • Section of Hepatobiliary Diseases and Department of Pathology, University of Florida College of Medicine, Gainesville, Florida
    • ,
  • Gregory Y. Lauwers

      Affiliations

    • Section of Hepatobiliary Diseases and Department of Pathology, University of Florida College of Medicine, Gainesville, Florida
    • ,
  • Johnson Y.N. Lau

      Affiliations

    • Department of Antiviral Therapy, Schering Plough Research Institute, Kenilworth, New Jersey
    • ,
  • Gary L. Davis

      Affiliations

    • Section of Hepatobiliary Diseases and Department of Pathology, University of Florida College of Medicine, Gainesville, Florida

Received 7 October 1999 ,Accepted 7 December 1999.

References 

  1. Tong MJ, el-Farra NS, Reikes AR, Co RL. Clinical outcomes after transfusion-associated hepatitis C. N Engl J Med. 1995;332:1463–1466
  2. Darby SC, Ewart DW, Giangrande PFL, Spooner RJ, Rizza CR, Dusheiko GM, et al. Mortality from liver cancer and liver disease in haemophilic men and boys in UK given blood products contaminated with hepatitis C. Lancet. 1997;350:1425–1431
  3. National Institutes of Health . National Institutes of Health Concensus Development Conference Panel statement: management of hepatitis C. Hepatology. 1997;26(suppl 1):2S–10S
  4. Fiorentino DF, Zlotnick A, Mosmann TR, Howard M, O'Garra A. IL-10 acts on the antigen presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146:3444–3451
  5. Nelson DR, Lau JYN. Pathogenesis of hepatocellular damage in chronic hepatitis C virus infection. Clin Liver Dis. 1997;1:515–527
  6. Tilg H, Wilmer A, Vogel W, Herold M, Nolchen B, Judmaier G, et al. Serum levels of cytokines in chronic liver diseases. Gastroenterology. 1992;103:264–274
  7. Nelson DR, Lim HL, Marousis CG, Fang JW, Davis GL, Shen L, et al. Activation of tumor necrosis–α system in chronic hepatitis C virus infection. Dig Dis Sci. 1997;42:2487–2494
  8. Napoli J, Bishop A, McGuinness PH, Painter DM, McCaughan GW. Progressive liver injury in chronic hepatitis C infection correlates with increased intrahepatic expression of Th1-associated cyto-kines. Hepatology. 1996;24:759–765
  9. Arai T, Hiromatsu K, Kobayashi N, Takano M, Ishida H, Nimura Y, et al. IL-10 is involved in the protective effect of dibutyryl cyclic adenosine monophosphate on endotoxin-induced inflammatory liver disease. J Immunol. 1995;155:5743–5749
  10. Louis H, Le Moine O, Peny M-O, Quertinmont E, Fokan D, Goldman M, et al. Production and role of interleukin-10 in concanavalin A–induced hepatitis in mice. Hepatology. 1997;25:1382–1389
  11. Nagaki M, Tanaka M, Sugiyama A, Ohnishi H, Moriwaki H. Interleukin-10 inhibits hepatic injury and tumor necrosis factor–α and interferon-γ mRNA expression induced by staphylococcal enterotoxin B or lipopolysacharide in galactosamine-sensitized mice. J Hepatol. 1999;31:815–824
  12. Davis GL, Lau JYN, Urdea MS, Neuwald PD, Wilber JC, Lindsay K, et al. Quantitative detection of hepatitis C virus RNA by a solid-phase signal amplification method. Definition of optimal conditions for specimen collection and clinical application in interferon-treated patients. Hepatology. 1994;19:1337–1341
  13. Lau JYN, Davis GL, Brunson ME, Qian KP, Lin HJ, Quan S, et al. Hepatitis C virus infection in renal transplant recipients. Hepatology. 1993;18:1027–1031
  14. Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B, et al. Classification of hepatitis C into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. J Gen Virol. 1993;74:2391–2399
  15. Gerlach JT, Diepolder H, Pape GR. Determination of hepatitis C virus-specific CD4+ T-cell activity in PBMC. In:  Lau JYN editors. Methods in molecular medicine. Volume 19:Totowa, NJ: Humana; 1998;p. 413–422 Hepatitis C protocols
  16. Nelson DR, Marousis CG, Davis GL, Rice CM, Wong J, Houghton M, et al. The role of hepatitis C virus–specific cytotoxic T lymphocytes in chronic hepatitis C. J Immunol. 1997;158:1473–1481
  17. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. III. Validity tests for the single-hit Poisson model. J Immunol Methods. 1984;72:29–40
  18. Ishak K, Baptista A, Bianchi L, Callea F, DeGroot J, Gudat F, et al. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22:696–699
  19. McHutchinson JG, Gordon SC, Schiff ER, Shiffman ML, Lee WM, Rustgi VK, et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med. 1998;339:1458–1492
  20. Poynard T, Marcellin P, Lee S, Niederau C, Minuk GS, Ideo G, et al. Randomized trial of interferon alfa-2b and ribavirin for 48 weeks or for 24 weeks versus interferon alfa-2b plus placebo for 48 weeks for treatment of chronic hepatitis C virus. Lancet. 1998;352:1426–1432
  21. Poynard T, Bedossa P, Chevallier M, Mathurin P, Lemonnier C, Trepo C, et al. A comparison of three interferon alfa-2b regimens for the long-term treatment of chronic non-A, non-B hepatitis. N Engl J Med. 1995;332:1457–1462
  22. Wang SC, Ohata M, Schrum L, Rippe RA, Tsukamoto H. Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J Biol Chem. 1998;273:302–308
  23. Reitamo S, Remitz A, Tamai K, Uitto J. Interleukin 10 modulates type 1 collagen and matrix metalloprotease gene expression in cultured human skin fibroblasts. J Clin Invest. 1994;94:2489–2492
  24. Louis H, Le Moine O, Peny M-O, Quertinmont E, Fokan D, Goldman M, et al. Production and role of interleukin-10 in concanavalin A–induced hepatitis in mice. Hepatology. 1997;25:1382–1389
  25. Thompson K, Maltby J, Fallowfield J, Mcaulay M, Millward-Sadler H, Sheron N. Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis. Hepatology. 1998;28:1597–1606

☆ Address requests for reprints to: David R. Nelson, M.D., Section of Hepatobiliary Diseases, Box 100214, University of Florida College of Medicine, Gainesville, Florida 32610-0214. e-mail: nelsodr@medicine.ufl.edu; fax: (352) 392-7393.

☆☆ Supported by a grant from Schering Plough Research Institute and the Clinical Research Center at the University of Florida (5M01RR00082); and grants from the National Institutes of Health (K08-DK2595), Glaxo Wellcome Institute for Digestive Health Clinical Research Award, and the American Digestive Health Foundation Innovative Seed Grant in Clinical Research in Liver Disease (to D.R.N.).

PII: S0016-5085(00)70134-X

Gastroenterology
Volume 118, Issue 4 , Pages 655-660 , April 2000

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