Skip to main content
Log in

IL-1β and TNF-α produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C

  • Liver: Infectious, Inflammatory, And Metabolic Disorders
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

We investigated the spontaneous and phytohemagglutinin-stimulated production of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) by peripheral blood mononuclear cells in patients with chronic hepatitis C during treatment with interferon-α (IFN-α). Spontaneous productions of these were significantly higher in patients with chronic hepatitis C than in healthy subjects. For patients prescribed interferon, stimulated production of TNF-α was significantly higher in complete responders than in partial responders, but the differences were small between the other cytokine levels and outcome of IFN treatment. Spontaneous production of these cytokines was higher in patients with genotype III with complete response than in genotype III patients with a partial response, but this was not the case in patients with genotype II. There was a negative correlation between these cytokines and histological activity index. Spontaneous production of cytokines was decreased only in complete responders after the administration of interferon. These data suggest that the elevated production of cytokines in patients with chronic hepatitis C may be due to host response to the virus, and monitoring cytokines along with alanine aminotransferase and hepatitis C virus RNA during treatment may provide more precise information of the effectiveness of therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Arai K, Lee F, Miyajima A, Miyataka S, Argi N, Yokota T: Cytokines: Coordinators of immune and inflammatory responses. Annu Rev Biochem 59:783–836, 1990

    PubMed  Google Scholar 

  2. Dinarello CA, Mier JW: Current concepts, lymphokines. N Engl J Med 317:940–945, 1987

    PubMed  Google Scholar 

  3. Ozyilkan E, Tatar G, Hacibektasoglu A, Kayhan B, Telatar H: Impaired lipopolysaccharide-induced interleukin-1-beta production in patients with anti-hepatitis C virus antibody-positive chronic liver disease. Scand J Gastroenterol 29:280–283, 1994

    PubMed  Google Scholar 

  4. Muller C, Knoflach P, Zielinski CC: Reduced production of immunoreactive interleukin-1 by peripheral blood monocytes of patients with acute and chronic viral hepatitis. Dig Dis Sci 38:477–481, 1993

    PubMed  Google Scholar 

  5. Anastassakos C, Alexander GJM, Wolstencroft RA, Avery JA, Portmann BG, Panayi GS, Dumonde DC, Eddleston ALWF, Williams R: Interleukin-1 and interleukin-2 activity in chronic hepatitis B virus infection. Gastroenterology 94:999–1005, 1988

    PubMed  Google Scholar 

  6. 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 10:769–773, 1989

    PubMed  Google Scholar 

  7. Tilg H, Wilmer A, Vogel W, Herold M, Nolchen B, Judmaier G, Huber C: Serum levels of cytokines in chronic liver diseases. Gastroenterology 103;264–274, 1992

    PubMed  Google Scholar 

  8. Lazzari FD, Fabris P, Floreani A, Bortolami M, Venturi C, Chiaramonte M, Naccarato R: Tumor necrosis factor-alpha behavior in serum during recombinant-alpha-2b-interferon treatment of chronic viral hepatitis. Eur J Gastroenterol Hepatol 6:625–628, 1994

    Google Scholar 

  9. Daniels HM, Meager A, Eddelston ALWF, Alexander GJM, Williams R: Spontaneous production of tumor necrosis factor alpha and interleukin-1 beta during interferon-alpha treatment of chronic HBV infection. Lancer 335:875–877, 1990

    Google Scholar 

  10. Dinarello CA: Interleukin-1 and its biologically related cytokines. Adv Immunol 44:153–205, 1989

    PubMed  Google Scholar 

  11. Oppenheim JJ, Kovaks EJ, Matsushima K, Durum SK: There is more than one interleukin 1. Immunol Today 7:45–56, 1986

    Google Scholar 

  12. 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 138:1786–1790, 1987

    PubMed  Google Scholar 

  13. Wong GHW, Goeddel DV: Tumor necrosis alpha and beta inhibit virus replication and synergize with interferon. Nature 323:819–822, 1986

    PubMed  Google Scholar 

  14. Mestan J, Digel W, Mittnacht S: Antiviral effects of recombinant tumor necrosis factorin vitro. Nature 323:816–819, 1986

    PubMed  Google Scholar 

  15. Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie AM, Peters M, Waggoner JG, Park Y, Jones EA: Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon. N Engl J Med 315:1575–1578, 1986

    PubMed  Google Scholar 

  16. Hayashi J, Nakashima K, Noguichi A, Hirata M, Akazawa K, Kashiwagi S: Antiviral effect of interferon therapy for patients with chronic hepatitis C. Antiviral Chem Chemother 3:305–309, 1992

    Google Scholar 

  17. Hayashi J, Ohmiya M, Kishihara Y, Tani Y, Kinukawa N, Ikematsu H, Kashiwagi S: A statistical analysis of predictive factors of response to human lymphoblastoid interferon in patients with chronic hepatitis C. Am J Gastroenterol 89:2151–2156, 1994

    PubMed  Google Scholar 

  18. Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, Kiernan TW, Wollman J: Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1:431–435, 1981

    PubMed  Google Scholar 

  19. Okamoto H, Sugiyama Y, Okada S, Kurai K, Akahane Y, Sugai Y, Tanaka T, Satoh K, Tsuda F, Miyakawa Y, Mayumi M: Typing hepatitis C virus by polymerase chain reaction with type-specific primers: Application to clinical surveys and tracing infectious sources. J Gen Virol 73:673–679, 1992

    PubMed  Google Scholar 

  20. Kaneko S, Murakami S, Unoura M, Kobayashi K: Quantitation of hepatitis C virus RNA by competitive polymerase chain reaction. J Med Virol 37:278–282, 1992

    PubMed  Google Scholar 

  21. Tanaka K, Ishikawa E, Ohmoto Y, Hirai Y:In vitro production of human interleukin 1α and interleukin 1β by peripheral blood mononuclear cells examined by sensitive sandwitch enzyme immunoassay. Eur J Immunol 17:1527–1530, 1989

    Google Scholar 

  22. Takehara T, Hayashi N, Mita E, Hagiwara H, Ueda K, Katayama K, Kasahara A, Fusamoto H, Kamada T: Detection of the minus strand of hepatitis C virus RNA by reverse transcription and polymerase chain reaction: Implications for hepatitis C virus replication in infected tissue. Hepatology 15:387–390, 1992

    PubMed  Google Scholar 

  23. Deviere J, Content J, Denys C, Vandenbussche P, Schandene L, Wybran J, Dupont E: Excessivein vitro bacterial lipopolysaccharide-induced production of monokines in cirrhosis. Hepatology 11:628–634, 1990

    PubMed  Google Scholar 

  24. Di Bisceglie A, Hoofnagle JH: Therapy of chronic hepatitis C with alpha-interferon: The answer? Or more questions? Hepatology 13:601–603, 1991

    PubMed  Google Scholar 

  25. Camps J, Crisostomo S, Garcia-Granero M, Riezu-Boj JI, Civeira MP, Prieto J: Prediction of the response of chronic hepatitis C to interferon alpha: A statistical analysis of pretreatment variables. Gut 34:1714–1717, 1993

    PubMed  Google Scholar 

  26. Noguchi A, Hayashi J, Nakashima K, Hirata M, Ikematsu H, Kashiwagi S: HBsAg subtypes among HBsAg carriers in Okinawa, Japan: Evidence of an important relationship in seroconversion from HBeAg to anti HBe. J Infect 28:141–150, 1994

    PubMed  Google Scholar 

  27. Kobayashi Y, Watanabe S, Konishi M, Yokoi M, Kakehashi R, Kaito M, Kondo M, Hayashi Y, Jimori T, Suzuki S: Quantitation and typing of serum hepatitis C virus RNA in patients with chronic hepatitis C treated with interferon-beta. Hepatology 18:1319–1325, 1993

    PubMed  Google Scholar 

  28. Tilg H, Mier JW, Vogel W, Aulitzky WE, Wiedermann CJ, Vannier E, Huber C, Dinarello CA: Induction of circulating IL-1 receptor antagonist by IFN treatment. J Immunol 150:4687–4692, 1993

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kishihara, Y., Hayashi, J., Yoshimura, E. et al. IL-1β and TNF-α produced by peripheral blood mononuclear cells before and during interferon therapy in patients with chronic hepatitis C. Digest Dis Sci 41, 315–321 (1996). https://doi.org/10.1007/BF02093821

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02093821

Key words

Navigation