Advertisement

Biotherapy

, Volume 7, Issue 3–4, pp 151–159 | Cite as

Cytokines in the treatment of virus infections

  • N. B. Finter
Article

Abstract

The interferon (IFN) system consists of both the formation of the various IFN proteins, and the diverse cellular responses which these induce: these result from the intracellular changes which follow their binding to a specific cell surface receptor.

There is only a single human gamma, omega and beta IFN; in contrast, there are 13 closely related chemical species (“subtypes”) of human alpha IFN, which are nevertheless chemically and biologically distinct.

IFN preparations made from mass cultured human cells or by using recombinant DNA techniques are now readily available for clinical use. IFN have a major role in the defence of the body against virus infections. In acute virus infections, preformed exogenous IFN cannot be given soon enough to be of value. However, IFN-α and IFN-β have proved of considerable value in some chronic virus infections, particularly chronic virus hepatitis and chronic papillomavirus infections. The doses routinely used are associated with both acute and chronic toxic side effects. Also, some patients form specific neutralising antibodies against the particular IFN preparation injected, which may abrogate all the benefits of the treatment. Nevertheless, IFN are now established as agents for use in routine medical practice.

Key words

Interferons IFN-α subtypes chronic virus infections hepatitis viruses papillomaviruses 

Abbreviations

TNF

Tumour necrosis factor

IL-6

Interleukin-6

eIF2

The protein initiation factor

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Finter NB, Chapman S, Dowd P, Johnston JM, Manna V, Sarantis N, Sheron N, Scott G, Phua S, Tatum PB. The use of Interferon-α in virus infections. Drugs 1991; 42: 749–765.PubMedGoogle Scholar
  2. 2.
    Trying SK. Introduction to the clinical uses of interferons. In: Baron S, Coppenhaver DH, Dianzani F, Fleischmann WR, Hughes TK, Klimpel GR, Niesel DW, Stanton GC, Tyring SK, eds. Interferon: principles and medical applications. Galveston, Tx: University of Texas Medical Branch 1992: 399–407.Google Scholar
  3. 3.
    Henco K, Brosius J, Fujisawa A, Fujisawa J-I, Haynes JR, Hochstadt J, Kovacic T, Pasek N, Schambock A, Schmid J, Todokoro K, Walchli M, Nagata S, Weissmann C. Structural relationship of human interferon alpha genes and pseudogenes. J Mol Biol 1985; 185: 227–260.PubMedGoogle Scholar
  4. 4.
    Diaz M, Allen G. Nomenclature of the human interferon genes. J interferon Res. 1993; 13: 61–62.PubMedGoogle Scholar
  5. 5.
    Weck PK, Apperson S, Hay L, Stebbing N. Comparison of the antiviral activities of various cloned human interferon-α subtypes in mammalian cell cultures. J Gen Virol 1981; 57: 233–237.PubMedGoogle Scholar
  6. 6.
    Zoon K, Zur Nedden DL, Enterline JC, Manischewitz JF, Dyer DR, Boykins RA, Bekisz J, Gerrard TL. Chemical and biological characterisation of natural human lymphoblastoid interferon alphas. In: Cantell K. Schellekens H, eds. The biology of the interferon system, 1986. Amsterdam: Martinus Nijhoff, 1987: 567–569.Google Scholar
  7. 7.
    Finter NB. Why are there so many subtypes of alphainterferons? J Gen Virol 1991; 185–194.Google Scholar
  8. 8.
    Tanaka T, Taniguchi T. Cytokine gene regulation: regulatory cis-elements and DNA binding factors involved in the interferon system. Adv Immunol 1992; 52: 263–279.PubMedGoogle Scholar
  9. 9.
    Revel M, Chebath J. Interferon-activated genes. Trends in Biol Sci 1986; 11: 166–170.Google Scholar
  10. 10.
    Hovanessian AG. Interferon-induced and double stranded RNA-activated enzymes: a specific protein kinase and 2′, 5′-Oligoadenylate synthetase. J Interferon Res 1991: 11: 199–205.PubMedGoogle Scholar
  11. 11.
    Pavlovic J, Staehli P. The antiviral potential of Mx proteins. J Interferon Res 1991; 11: 215–219.PubMedGoogle Scholar
  12. 12.
    Rhodes J., Ivanyi I, Cozens P. Antigen presentation by human monocytes: effects of modifying major histocompatability complex class II antigen expression and interleukin 1 production by using recombinant interferons and corticosteroids. Eur J Immunol 1986; 16: 370–375.PubMedGoogle Scholar
  13. 13.
    Gewert D, Finter NB. Antiviral effects of interferons: studies in animals and at the cellular level. In: Baron S, Coppenhaver DH, Dianzani F, Fleischmann WR, Hughes TK, Klimpel GR, Niesel DW, Stanton GC, Tyring SK, eds. Interferon: principles and medical applications. Galveston, Tx: University of Texas Medical Branch, 1992: 289–297.Google Scholar
  14. 14.
    Gresser I, Tovey MG, Bandu MT, Maury C, Brouty-Boye D. Role of interferon in the pathogenesis of virus disease as demonstrated by the use of anti-interferon serum. 1. Rapid evolution of encephalomyocarditis virus infection. J Exp Med 1976; 144: 1305–1315.PubMedGoogle Scholar
  15. 15.
    Standardization of interferons. Geneva: World Health Organisation Technical report series 1983: No. 687 Annex 1: 35–60. 1985: No. 725: 28–64. 1988: No. 771: 37–87.Google Scholar
  16. 16.
    Isaacs A, Lindenmann, J. Virus interference. I. The interferon. Proc Roy Soc ser B 1957; 147: 258–267.Google Scholar
  17. 17.
    Strander H, Cantell K. Production of interferon by human leukocytes in vitro. Ann Med Exp Biol Fenn 1966; 44: 265–273.PubMedGoogle Scholar
  18. 18.
    Hosai H, Miyake K, Yamanaka M. The interferon a2 gene in Japanese patients with chronic viral hepatitis who developed antibodies after recombinant a2A treatment. Abstr Sci Mtg Internatl. Assoc. for the study of the Liver, Brighton, 1992; June 3–6, 113.Google Scholar
  19. 19.
    Gewert D, Salom C, Barber K, Macbride S, Cooper H, Lewis A, Wood J, Crowe S. Analysis of interferon-α2 sequences in human genomic DNA. J Interferon Res 1993; 13: 27–231.Google Scholar
  20. 20.
    Finter NB. Interferons and inducers in vivo: I. antiviral effects in experimental animals. In: Finter NB, ed. Interferons and interferon inducers. Amsterdam: North-Holland, 1973: 295–362.Google Scholar
  21. 21.
    Gresser I, Bourali C, Thomas MT, Falcoff E. Effect of repeated inoculation of interferon preparations on infections of mice with encephalomyocarditis virus. Proc Soc Exp Biol Med 1968; 127: 491–496.PubMedGoogle Scholar
  22. 22.
    Hilfenhaus J, Polastri GD. Antiviral effects of interferons in animals. In: Finter NB and Oldham PK, eds. Interferon 4. Amsterdam: Elsevier, 1973: 3–21.Google Scholar
  23. 23.
    Finter NB. Interferon as an antiviral agent in vivo: quantitative and temporal aspects of the protection of mice against Semliki forest virus. Brit J Exp Pathol 1966; 47: 361–371.Google Scholar
  24. 24.
    McGill JI, Collins P, Cantell K, Jones BR, Finter NB. Optimal schedules for use of interferon in the corneas of rabbits with herpes simplex keratitis. J Infect Dis 1976; 133: A13-A19.PubMedGoogle Scholar
  25. 25.
    Gresser I, Tovey MG, Maury C. Efficacy of exogenous treatment with interferon after the onset of multiplication of vesicular stomatitis virus in the brains of mice. J Gen Virol 1975; 27: 395–403.PubMedGoogle Scholar
  26. 26.
    Heremans H, Billiau A, De Somer P. Interferon in experimental viral infections in mice: tissue interferon levels resulting from the virus infection and from exogenous interferon therapy. Infect Immun 1980; 30: 513–522.PubMedGoogle Scholar
  27. 27.
    Gresser I, Coppey J, Bourali C. Interferon and mouse leukemia. VI. The effect of interferon preparations on the lymphoid leukemia of AKR mice. J Nat Cancer Instit 1969; 43: 1083–1089.Google Scholar
  28. 28.
    Bottomley JM, Toy JL. Clinical side effects and toxicities of interferons. In: Finter NB and Oldham RK, eds. Interferon 4. Amsterdam: Elsevier, 1973: 155–180.Google Scholar
  29. 29.
    Kramer P, Ten Kate FWJ, Bijenen AB, Jeekel J, Weimar W. Recombinant leukocyte interferon A induces steroid-resistant acute vascular rejection episodes in renal transplant recipients. Lancet 1984; i: 989–990.Google Scholar
  30. 30.
    Greenberg HB, Pollard R, Lutwick L, Gregory P, Robinson W, Merigan TC. Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. N Engl J Med 1976; 295: 517–522.PubMedGoogle Scholar
  31. 31.
    Di Bisceglie AM, Rustgi VK, Kassianides C, Lisker-Melman M, Park Y, Waggoner JG, Hoofnagle J. Therapy of chronic hepatitis B with recombinant alpha and gamma interferon. Hepatol 1990; 11: 266–270.Google Scholar
  32. 32.
    Hoofnagle JH. Interferon therapy of viral hepatitis. In: Baron S, Coppenhaver DH, Dianzani F, Fleischmann WR, Hughes TK, Klimpel GR, Niesel DW, Stanton GC, Tyring SK, eds. Interferon: principles and medical applications. Galveston, Tx: University of Texas Medical Branch 1992: 433–462.Google Scholar
  33. 33.
    Kanai K, Kako M, Okamoto H. HCV genotypes in chronic hepatitis C and response to interferon. Lancet 1992; 339: 1543.Google Scholar
  34. 34.
    Ideo, G., Bellati, G., Pedraglio, E., Leandro, G. One year of therapy of non A, non B/C chronic hepatitis with recombinantα-2a interferon (r-IFN) or lymphoblastoidα interferon (LIFN). Abstr. 25th meeting Europ Assoc Study of Liver Dis. J Hepatol 1990; 14 suppl 2: S31.Google Scholar
  35. 35.
    Cimino L, Citarella C, Nardone G, Budillon G. Lymphoblastoid interferon in chronic hepatitis C patients, ‘non-responders’ to recombinant interferon-α (rIFN-α). Hepatol 1992; 14: 419–420.Google Scholar
  36. 36.
    Healy GB, Gelber RD, Trowbridge AL, Grundfast KM, Ruben RJ, Price KN. Treatment of recurrent respiratory papillomatosis with human leucocyte interferon. N Engl J Med 1988; 319: 401–407.PubMedGoogle Scholar
  37. 37.
    Kashima HK, Leventhal BG, Dedo H, Gardiner L, McCabe BF, Richardson M, Whisnant J, Clark K, Donovan D, Goepfert H, Mounts P, Singleton G, Wold D, Cohen F, Fearon B, Lusk R, Muntz H, Weck P, Yonkers A. Interferon-alfa N1 (Wellferon) in juvenile onset recurrent respiratory papillomatosis: results of a randomized study in twelve collaborative institutions. Laryngoscope 1988; 98: 334–340.PubMedGoogle Scholar
  38. 38.
    Leventhal BG, Kashima HK, Mounts P, Thurmond L, Chapman S, Buckley S, Wold D. and the Papilloma Study Group. Long-term response of recurrent respiratory papillomatosis to treatment with lymphoblastoid interferon Alfa-N1. N Engl J Med 1991; 325: 613–617.PubMedGoogle Scholar
  39. 39.
    Gall SA, Hughes RN, Mounts P, Segriti A, Weck PK, Whisnant JK. Efficacy of human lymphoblastoid interferon in the therapy of resistant condyloma acuminata. Obstet Gynecol 1986; 67: 643–651.PubMedGoogle Scholar
  40. 40.
    Friedman-Kien AE, Eron LJ, Conant M, Growdon W, Badiak H, Bradstreet PW, Fedorczyk MS, Trout JR, Plasse TF. Natural interferon alfa for treatment of condylomata acuminata. J Am Med Assoc 1988; 259: 533–538.Google Scholar
  41. 41.
    Condyloma international collaborative study group. Recurrent condyloma acuminata treated with recombinant interferon alfa-2a: a multicenter double-blind placebo controlled clinical trial. J Am Med Assoc 1991; 265: 2684–2687.Google Scholar
  42. 42.
    Gibson JR. The treatment of viral warts. J Antimicrob Chemother 1988; 21: 391–393.PubMedGoogle Scholar
  43. 43.
    Berman B, Davis-Reed L, Silverstein L. Treatment verruca vulgaris with anα2 interferon. J Infect Dis 1986; 154: 328–330.PubMedGoogle Scholar
  44. 44.
    Hartshorn, KL, Vogt MW, Chou TC, et al. Synergistic inhibition of human immune virus in vitro by azidothymidine (AZT) and recombinant alpha-A interferon. Antimicrob Agents Chemother 1987; 31: 168–172.PubMedGoogle Scholar
  45. 45.
    De Wit R. Kaposi's sarcoma and AIDS. In: Baron S, Coppenhaver DH, Dianzani F, Fleischmann WR, Hughes TK, Klimpel GR, Niesel DW, Stanton GC, Tyring SK, eds. Interferon: principles and medical applications. Galveston, Tx: University of Texas medical Branch 1992: 475–485.Google Scholar
  46. 46.
    Merigan TC, Gallagher JG, Pollard RB, Arvin AM. Shortcourse human leukocyte interferon in treatment of herpes zoster in patients with cancer. Antimicrob Agents Chemother 1981; 19: 193–195.PubMedGoogle Scholar
  47. 47.
    Scientific Committee on Interferon. Experiments with interferon in man. Lancet 1965; i: 505–506.Google Scholar
  48. 48.
    Merigan TC, Reed SE, Tyrrell DAJ. Inhibition of respiratory virus infection by locally applied interferon. Lancet 1973; i: 563–567.Google Scholar
  49. 49.
    Hayden FG, Mills SE, Johns ME. Human tolerance and histopathologic effects of long term administration of intranasal interferon-alpha 2. J Infect Dis 1983; 148: 914–921.PubMedGoogle Scholar
  50. 50.
    Douglas RB, Moore BW, Miles HB. Prophylactic efficacy of intranasal alpha2 interferon against rhinovirus infections in the family setting. N Engl J Med 1986; 314: 65–70.PubMedGoogle Scholar
  51. 51.
    Jones BR, Coster DJ, Falcon MG, Cantell K. Topical therapy of ulcerative herpetic keratitis with human interferon. Lancet 1976; ii: 128.Google Scholar
  52. 52.
    Sundmacher R, Neumann-Haefelin D, Cantell K. Interferon treatment of dendritic keratitis. Lancet 1976; i: 1406–1407.Google Scholar
  53. 53.
    De Koning EWJ, van Bijsterveld OP, Cantell K. Combination therapy for dendritic keratitis with acyclovir andα-interferon. Arch Ophthalm 1983; 101: 1866–1868.Google Scholar
  54. 54.
    Hirsch MS, Schooley RT, Cosimi AB, Russell PS, Delmonico FL, Tolkoff-Rubin NE, Herrin JT, Cantell K, Farrell M-L, Rota TR, Rubin RH. Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal-transplant recipients. N Engl J Med 1983; 308: 1489–1493.PubMedGoogle Scholar
  55. 55.
    Milella M, Antonelli A, Santantonio T, Currenti M, Monno L, Mariano N, Angarano G, Dianzani F, Pastore G. Neutralising antibodies to recombinant alpha-interferon and response to therapy in chronic hepatitis C virus infection. Liver 1993; 13: 146–150.PubMedGoogle Scholar
  56. 56.
    Von Wussow P, Jakschies D, Freund M, Hehlman R, Brockhaus F, Hochkeppel H. Treatment of anti-recombinant interferon-alpha 2 antibody positive CML patients with natural interferon-alpha. Br J Haematol 1991; 78: 210–216.PubMedGoogle Scholar
  57. 57.
    Von Wussow P, Pralle H, Hochkeppel H-K, Jakschies D, Sonnen S, Schmidt H, Muller-Rosenau D, Franke M, Haferlach T, Zwingers T, Rapp U, Deicher H. Effective natural interferon-α therapy in recombinant interferon-α-resistant patients with hairy cell leukaemia. Blood 1991; 78: 38–43.PubMedGoogle Scholar
  58. 58.
    McSweeney EN, Giles FJ, Worman CP, Jewel AP, Tsakona CP, Hoffbrand AV, Mehta AB, Newland AC, Cawley JC, Galvani D, Singer CDJ, Grant IR, Norfolk DR, Goldstone AH. Recombinant interferon alfa 2a in the treatment of patients with early stage B chronic lymphocytic leukaemia. Brit J Haematol 1993; 85: 77–83.Google Scholar
  59. 59.
    Antonelli G, Currenti M, Turriziani O, Dianzani F. Neutralising antibodies to interferon-α: relative frequency in patients treated with different interferon preparations J Infect Dis 1991; 163: 882–885.PubMedGoogle Scholar
  60. 60.
    Lok ASF, Lai C-L. Incidence, neutralising activity and clinical significance of interferon antibodies in chronic hepatitis B patients receiving recombinant a-interferons. In: Hollinger FB. Margolis HS, eds. Viral hepatitis and liver disease. Baltimore: Williams and Wilkins, 1991: 643–645.Google Scholar
  61. 61.
    Lok ASF, Lai C-L, Leung EK-Y. Interferon antibodies may negate the antiviral effects of recombinantα-interferon treatment in patients with chronic hepatitis B virus infection. Hepatol 1990; 12: 1266–1270.Google Scholar
  62. 62.
    Gianelli G, Antonelli G, Fera G, Dianzani F. Schiraldi 0. 2′, 5′-Oligoadenylate synthetase activity as a responsive marker during interferon therapy for chronic hepatitis C. J Interferon Res 1993; 13: 57–60.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • N. B. Finter
    • 1
  1. 1.SevenoaksUK

Personalised recommendations