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The Potential Role of Cytokines in the Treatment of Viral Infections

  • Review Article
  • Disease Treatment Review
  • Published:
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Summary

A recent approach to the prevention or control of viral diseases has been to consider the use of cytokines as potential therapies. This has increased with the recent commercial availability of recombinant protein cytokines.

The cytokines that have been studied, both experimentally and in humans, as antiviral therapies include interleukin-1, -2, -6 and -7, interferon-α, -β and -γ, tumour necrosis factor-α and -β, and the colony-stimulating factors. This article covers the therapeutic use of these cytokines in all important virus diseases, with particular emphasis on human immunodeficiency virus infection, including the related Kaposi’s sarcoma.

Significant antiviral effects have been reported for most of these cytokines. Beneficial effects are particularly apparent when they are used in combination with the more traditional antiviral agents.

The cytokines have extraordinarily broad biological functions. Some of these functions may reverse the desired antiviral action and may indeed bring about an enhancement or activation of viral infections, depending on how they are used. Such effects have been reported with some of the cytokines discussed in this review.

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References

  1. Rees RC. Cytokines as biological response modifiers. J Clin Pathol 1992; 45: 93–8

    PubMed  CAS  Google Scholar 

  2. Dinarello CA. Interleukin-1 and its biologically related cytokines. In: Cohen S, editor, Lymphokines and the immune response. Boca Raton: CRC Press, 1990: 145–79

    Google Scholar 

  3. Ruggiero V, Antonelli G, Gentile M, et al. Comparative study on the antiviral activity of tumor necrosis factor (TNF)-alpha, lymphotoxin/TNF-beta, and IL-1 in WISH cells. Immunol Lett 1989; 21: 165–9

    PubMed  CAS  Google Scholar 

  4. Van Damme J, DeLey M, VanSnick J, et al. The role of interferon-β1 and the 26-kDa protein (interferon-β2) as mediators of the antiviral effect of interleukin 1 and tumor necrosis factor. J Immunol 1987; 139: 1867–72

    PubMed  Google Scholar 

  5. Kohase M., Zhang YH, Lin JK, et al. Interleukin-1 can inhibit interferon-beta synthesis and its antiviral action: comparison with tumor necrosis factor. J Interferon Res 1988; 8: 559–70

    PubMed  CAS  Google Scholar 

  6. Leshem B, Dekel R, Bercovier H, et al. Cytokine-induced resistance to microbial infections in normal, immunosuppressed and bone-marrow transplanted mice. Bone Marrow Transplant 1992; 9: 471–7

    PubMed  CAS  Google Scholar 

  7. Kuziel WA, Green WC. Interleukin-2. In: Thomson A, editor. The cytokine handbook. New York: Academic Press, 1991: 83–102

    Google Scholar 

  8. Whittington R, Faulds D. Interleukin-2. A review of its pharmacological properties and therapeutic use in patients with cancer. Drugs 1993; 46: 446–514

    PubMed  CAS  Google Scholar 

  9. Welted K, Ciobanun N, Kruger G, et al. Impaired interleukin-2 production in response to PHA and OKT3 antibody in male homosexuals with acquired immunodeficiency syndrome: in vitro restoration of T-cell proliferation by highly purified interleukin-2. In: Friedman-Kien AE, Laubenstein LJ, editors. AIDS, the epidemic of Kaposi’s sarcoma and opportunistic infections. New York: Masson Publishing, 1983: 199–205

    Google Scholar 

  10. Rook AH, Masur H, Lane HC, et al. Interleukin-2 enhances the depressed natural killer and cytomegalovirus-specific cytotoxic activities of lymphocytes from patients with the acquired immune deficiency syndrome. J Clin Invest 1983; 72: 398–403

    PubMed  CAS  Google Scholar 

  11. Devita VT, Broder S, Fauci AS, et al. Developmental therapeutics and the acquired immunodeficiency syndrome. Ann Intern Med 1987; 106: 568–76

    PubMed  Google Scholar 

  12. Lane HC, Siegel JP, Rook AH, et al. Use of interleukin-2 in patients with acquired immunodeficiency syndrome. J Biol Resp Mod 1984; 3: 512–6

    CAS  Google Scholar 

  13. Kaplan LD, Wofsy CB, Volberding PA. Treatment of patients with acquired immunodeficiency syndrome and associated manifestations. JAMA 1987; 257: 1367–74

    PubMed  CAS  Google Scholar 

  14. Volberding P, Moody DJ, Beardslee D, et al. Therapy of acquired immune deficiency syndrome with recombinant interleukin-2. AIDS Res Human Retroviruses 1987; 3: 115

    CAS  Google Scholar 

  15. Clark AGB, Holodniy M, Schwartz DH, et al. Decrease in HIV provirus in peripheral blood mononuclear cells during zidovudine and human rIL-2 administration. J AIDS 1992; 5: 52

    CAS  Google Scholar 

  16. Schwartz DH, Skowron G, Merigan TC. Safety and effects of interleukin-2 plus zidovudine in asymptomatic individuals infected with human immunodeficiency virus. J AIDS 1991; 4: 11–23

    CAS  Google Scholar 

  17. Bartlett JA, Blankenship K, Waskin H, et al. The therapeutic uses of interleukin-2 in patients with HIV infection. In: Proceedings of the VIIth International Conference on AIDS; 1991; Florence. Abstr. WB2154

    Google Scholar 

  18. Teppler H, Kaplan G, Smith KA, et al. Prolonged immunostimulatory effect of low-dose polyethylene glycol interleukin-2 in patients with human immunodeficiency virus type 1 infection. J Exp Med 1993; 177: 483–92

    PubMed  CAS  Google Scholar 

  19. Kovacs JA, Baseler M, DeWar R, et al. Immunologic enhancement in HIV-infected patients with intermittent interleukin-2 [abstract]. Proceedings of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy; 1993: 328

    Google Scholar 

  20. Zeidner NS, Rose LM, Mathiason-DuBard CK, et al. Zidovudine in combination with alpha interferon and interleukin-2 as prophylactic therapy for FeLV-induced immunodeficiency syndrome. J AIDS 1990; 3: 787–96

    CAS  Google Scholar 

  21. Mead JR, Burger RA, Yonk LJ, et al. Effect of human recombinant interleukin 2 on Punta Toro virus infections in C57BL/6 mice. Antiviral Res 1991; 15: 331–40

    PubMed  CAS  Google Scholar 

  22. Poli G, Bressler P, Kinder A, et al. Interleukin 6 induces human-immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor by transcriptional and post-transcriptional mechanisms. J Exp Med 1990; 172: 151–8

    PubMed  CAS  Google Scholar 

  23. Rosenwirth B, Besemer J. Quantitatively different effects of cytokines on chronic HIV-1 infection. Antiviral Res 1990; 3Suppl. 1: 95

    Google Scholar 

  24. Namen AE, Schmierer AE, March CJ, et al. B cell precursor growth-promoting activity. Purification and characterization of a growth factor active on lymphocyte precursors. J Exp Med 1988; 167: 988–1002

    PubMed  CAS  Google Scholar 

  25. Lu L, Zhou Z, Wu B, et al. Influence of recombinant human interleukin (IL)-7 on disease progression in mice infected with Friend virus complex. Int J Cancer 1992; 52: 261–5

    PubMed  CAS  Google Scholar 

  26. Isaacs A, Lindenmann J. Virus interference: I. The interferon. Proc R Soc Lond [Biol] 1957; 147: 258–67

    CAS  Google Scholar 

  27. Borden EC, Fall LA. Interferons: biochemical, cell growth, inhibitory and immunological effects. Prog Hematol 1981; 350: 1–64

    Google Scholar 

  28. Kornbluth RS, Ikl PS, Munis JR, et al. Interferons and bacterial lipopolysaccharide protect macrophage from productive infection by human immunodeficiency virus in vitro. J Exp Med 1989; 169: 1137–51

    PubMed  CAS  Google Scholar 

  29. Pitha PM, Wival NA, Fernie BF, et al. Effect of interferon on murine leukemia virus infection. IV. Formation of non-infectious virus in chronically infected cells. J Gen Virol 1979; 42: 467–80

    PubMed  CAS  Google Scholar 

  30. Aboud M, Kimchi R, Bakhanashvili M, et al. Intracellular production of virus particles and viral components in NIH/3T3 cells chronically infected with Moloney murine leukemia virus: effect of interferons. J Virol 1981; 40: 830–8

    PubMed  CAS  Google Scholar 

  31. Ho DD, Hartshorn KL, Rota TR, et al. Recombinant human interferon α-A suppresses HTLV-III replication in vitro. Lancet 1985; 1: 602–4

    PubMed  CAS  Google Scholar 

  32. Poli G, Orenstein JM, Kinder A, et al. Interferon-α but not AZT suppresses HIV expression in chronically infected cell lines. Science 1989; 244: 575–7

    PubMed  CAS  Google Scholar 

  33. Aboud M, Shoor R, Salzber S. An effect of interferon on the uncoating of murine leukemia virus not related to antiviral state. J Gen Virol 1980; 51: 425–9

    PubMed  CAS  Google Scholar 

  34. Bilello JA, Wivel NA, Pitha PM. Effect of interferon on the replication of mink cell focus-inducing virus in murine cells: synthesis, processing, assembly, and release of viral proteins. J Virol 1982; 43: 213–22

    PubMed  CAS  Google Scholar 

  35. Smith MS, Thresher RJ, Pagano JS. Inhibition of human immunodeficiency virus type I morphogenesis in T cells by a interferon. Antimicrob Agents Chemother 1991; 35: 62–7

    PubMed  CAS  Google Scholar 

  36. Friedman RM. Antiviral activity of interferons. Bacteriol Rev 1977; 41: 543–67

    PubMed  CAS  Google Scholar 

  37. Sen GC. Biochemical pathways in interferon action. Pharmacol Ther 1984; 24: 235–57

    PubMed  CAS  Google Scholar 

  38. Naso RB, Wu YC, Edbauer CA. Antiretroviral effect of interferon: proposed mechanism. J Interferon Res 1982; 2: 75–96

    PubMed  CAS  Google Scholar 

  39. Herberman RB, Djeu JY, Ortaldo JR, et al. Role of interferon with augmentation of natural and antibody-dependent cell-mediated cytotoxicity. Cancer Treat Rep 1978; 62: 1893–6

    PubMed  CAS  Google Scholar 

  40. Hartshorn KL, Vogt MW, Chou T-C, et al. Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant α-A interferon. Antimicrob Agents Chemother 1987; 31: 168–92

    PubMed  CAS  Google Scholar 

  41. Hartshorn KL, Sandstrom EG, Neumeyer D, et al. Synergistic inhibition of human T-cell lymphotropic virus type III replication in vitro by phosphonoformate and recombinant α-A interferon. Antimicrob Agents Chemother 1986; 30: 189–91

    PubMed  CAS  Google Scholar 

  42. Ito M, Baba M, Shigeta S, et al. Synergistic inhibition of human immunodeficiency virus type 1 replication in vitro by 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine and recombinant interferon. Antiviral Res 1991; 15: 323–30

    PubMed  CAS  Google Scholar 

  43. Johnson VA, Merrill DP, Chou T-C, et al. Human immunodeficiency virus type 1 inhibitory interactions between protease inhibitor Ro 31-8959 and zidovudine, 2′,3′-dideoxycytidine, or recombinant interferon αA against zidovudine-sensitive or -resistant HIV-1 in vitro. J Infect Dis 1992; 166: 1143–6

    PubMed  CAS  Google Scholar 

  44. Ruprecht RM, Chou TC, Chipty F, et al. Interferon-α and 3′-azido-3′-deoxythymidine are highly synergistic in mice and prevent viremia after acute retrovirus exposure. J AIDS 1990; 3: 591–600

    CAS  Google Scholar 

  45. Sidwell RW, Morrey JD, Okleberry KM, et al. Immunomodulator effects on Friend virus infection in genetically defined mice. Ann NY Acad Sci 1993; 685: 432–46

    PubMed  CAS  Google Scholar 

  46. Sidwell, RW, Morrey JD, Warren RP, et al. Effect of the combination of human recombinant interferon-α-A/D and 2′,3′-didehydro-2′,3′-dideoxythymidine (D4T) on murine retrovirus disease. Recent Adv Chemother 1993; in press

    Google Scholar 

  47. Zeidner NS, Myles MH, Mathiason-DuBard CK, et al. Alpha interferon (2b) in combination with zidovudine for the treatment of presymptomatic feline leukemia virus-induced immunodeficiency syndrome. Antimicrob Agents Chemother 1990; 34: 1749–56

    PubMed  CAS  Google Scholar 

  48. Fazely F, Haseltine WA, Rodger RF, et al. Post exposure chemoprophylaxis with ZDV or ZDV combined with interferon-αα: failure after inoculating rhesus monkeys with a high dose of SIV. J AIDS 1991; 4: 1093–97

    CAS  Google Scholar 

  49. Williams GJ, Colby CB. Recombinant human interferon-α suppresses the replication of HIV and acts synergistically with AZT. J Interferon Res 1989; 9: 709–18

    PubMed  CAS  Google Scholar 

  50. Kort JJ, Eiseman JL. Interferon-gamma: a potent antiviral agent targeting macrophages infected with LP-BM5 murine leukaemia virus, the causative agent of ‘AIDS’ in mice. Can J Infect Dis 1992; 3 (Suppl. B): 115B–122B

    Google Scholar 

  51. Lu L, Shen RN, Shou SZ, et al. Synergistic effect of human lactoferrin and recombinant murine interferon-γ on disease progression in mice infected with the polycythemia-inducing strain of the Friend virus complex. Int J Hematol 1991: 54: 117–24

    PubMed  CAS  Google Scholar 

  52. D’Onofrio C, Franzese O, Puglianiello A, et al. Antiviral activity of individual versus combined treatments with interferon α, β and γ on early infection with HTLV-I in vitro. Int J Immunopharmacol 1992; 14(6): 1069–79

    PubMed  Google Scholar 

  53. Krown SE, Real FX, Cunningham-Rundles S, et al. Preliminary-observations on the effect of recombinant leukocyte α interferon in homosexual men with Kaposi’s sarcoma. N Engl J Med 1983; 308: 1071–6

    PubMed  CAS  Google Scholar 

  54. Groopman JE, Gottlieb MS, Goodman J, et al. Recombinant α-2b interferon therapy for Kaposi’s sarcoma associated with acquired immune deficiency syndrome. Ann Intern Med 1984; 100: 671–6

    PubMed  CAS  Google Scholar 

  55. Heagy W, Groopman J, Schindler J, et al. Use of IFN-γ in patients with AIDS. J AIDS 1990; 3: 584–90

    CAS  Google Scholar 

  56. Dorr RT. Interferon-α in malignant and viral diseases: a review Drugs 1993; 45: 177–211

    CAS  Google Scholar 

  57. Krown SE. The role of interferon in the therapy of epidemic Kaposi’s sarcoma. Semin Oncol 1987; 14Suppl. 3: 27–33

    PubMed  CAS  Google Scholar 

  58. Lane HC, Feinberg J, Davey V, et al. Anti-retroviral effects of IFN-α in AIDS-associated KS. Lancet 1988; 2: 1218–22

    PubMed  CAS  Google Scholar 

  59. deWitt R, Schattenkerk JK, Boucher CA, et al. Clinical and virological effects of high-dose recombinant interferon-α in disseminated AIDS-related Kaposi’s sarcoma. Lancet 1988; 2: 1214–7

    Google Scholar 

  60. Evans, LM, Itri LM, Campion M, et al. Interferon-α 2a in the treatment of acquired immunodeficiency syndrome-related Kaposi’s sarcoma. J Immunother 1991; 10: 39

    PubMed  CAS  Google Scholar 

  61. Volberding PA, Mitsuyasu RT, Golando JP, et al. Treatment of Kaposi’s sarcoma with interferon α-2b. Cancer 1987; 59: 620

    PubMed  CAS  Google Scholar 

  62. Fischl MA, Gorowski E, Koch G, et al. Interferon α-n1 Wellferon in Kaposi’s sarcoma: single agent or combination with vinblastine. In: Stewart WE, Schellekens H, editors. The biology of the interferon system. Boston: Martinus Nijhoff, 1987: 355

    Google Scholar 

  63. De Wit R, Bakker PJM, Reiss P, et al. Temporary increase in serum β2-microglobulin during treatment with interferon-α for AIDS-associated Kaposi’s sarcoma. AIDS 1990; 4: 459–62

    PubMed  Google Scholar 

  64. De Wit R, Bakker PJM, Veenhof CHN, et al. Continued zidovudine and interferon-alpha therapy in Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS). Ann Int Med 1990; 112: 306–11

    PubMed  Google Scholar 

  65. Kovacs JA, Deyton L, Davey R, et al. Combined zidovudine and interferon-α therapy in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome (AIDS). Ann Int Med 1989; 111: 280

    PubMed  CAS  Google Scholar 

  66. Krown SE, Gold JWM, Niedzwiecki D, et al. Interferon-α with zidovudine: safety, tolerance and clinical and virologic effects in patients with Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome. Ann Int Med 1990; 112: 812

    PubMed  CAS  Google Scholar 

  67. Scadden DT, Bering HA, Levine JD, et al. Granulocyte-macrophage colony-stimulating factor mitigates the neutropenia of combined interferon α and zidovudine treatment of acquired immune deficiency syndrome-associated Kaposi’s sarcoma. J Clin Oncol 1991; 9: 802

    PubMed  CAS  Google Scholar 

  68. Lane HC, Davey V, Kovacs JA, et al. Interferon-α in patients with asymptomatic human immunodeficiency virus (HIV) infection: A randomized, placebo-controlled trial. Ann Int Med 1990; 112: 805–11

    PubMed  CAS  Google Scholar 

  69. Miles SA, Wang HJ, Cortes E, et al. Beta interferon therapy in patients with poor-prognosis Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS). A Phase II trial with preliminary evidence of antiviral activity and low incidence of opportunistic infections. Ann Int Med 1990; 112: 582–9

    PubMed  CAS  Google Scholar 

  70. Lane HC, Davey RT, Sherwin SA, et al. A phase I trial of recombinant human interferon-γ in patients with Kaposi’s sarcoma and acquired immunodeficiency syndrome (AIDS). J Clin Immunol 1989; 9: 351–61

    PubMed  CAS  Google Scholar 

  71. Parkin J, Eales LJ, Galazka AR, et al. Atopic manifestations in the acquired immune deficiency syndrome: response to recombinant interferon gamma. Br Med J 1987; 294: 1185–6

    CAS  Google Scholar 

  72. Yarchoan R, Mitsuya H, Broder S. AIDS therapy. Sci Am 1988; 258: 88

    Google Scholar 

  73. Fischl MA, Richman DD, Hansen N, et al. The safety and efficacy of zidovudine (AZT) in the treatment of mildly symptomatic human immunodeficiency virus type 1. Ann Int Med 1990; 11: 727

    Google Scholar 

  74. Lane HC, Falloon J, Walker RE, et al. Zidovudine in patients with human immunodeficiency virus (HIV) infection and Kaposi sarcoma. Ann Int Med 1989; 111: 41–50

    PubMed  CAS  Google Scholar 

  75. DeWit R, Reiss P, Bakker PJM, et al. Lack of activity of zidovudine in AIDS-associated Kaposi’s sarcoma. AIDS 1989; 3: 847–56

    CAS  Google Scholar 

  76. Eron LJ, Judson F, Tucker S, et al. Interferon therapy for condylomata acuminata. N Engl J Med 1986; 315: 1059–64

    PubMed  CAS  Google Scholar 

  77. Friedman-Kien A, Eron LJ, Conant M, et al. Natural interferon α for treatment of condylomata acuminata. JAMA 1988; 259: 533–8

    PubMed  CAS  Google Scholar 

  78. Reichman RC, Bonnez W. Intralesional interferons in the treatment of condyloma acuminata. In: Mills J, Corey L, editors. Antiviral chemotherapy: new directions for clinical application and research. Amsterdam: Elsevier, 1989: 143–7

    Google Scholar 

  79. Kirby P. Systemic interferon and combination therapy for genital warts. In: Mills J, Corey L, editors. Antiviral chemotherapy: new directions for clinical application and research. Amsterdam: Elsevier, 1989: 151–62

    Google Scholar 

  80. Androphy EJ, Dvoretzky I, Maluish AE, et al. Response of warts in epidermodysplasia verruciformis to treatment with systemic and intralesional alpha interferon. J Am Acad Dermatol 1984; 11: 197–202

    PubMed  CAS  Google Scholar 

  81. Reichman RC. Use of interferons for papilloma virus infections. In: Mills J, Corey L, editors. Antiviral chemotherapy: new directions for clinical application and research. Amsterdam: Elsevier, 1989; 44–9

    Google Scholar 

  82. Pifat, DY, Smith JT. Punta Toro virus infection of C57BL/6J mice: a model for phlebovirus-induced disease. Microb Pathog 1987; 3: 409–22

    PubMed  CAS  Google Scholar 

  83. Sidwell RW, Huffman JH, Smee DF, et al. Potential role of immunomodulators for treatment of phlebovirus infections of animals. NY Acad Sci 1992; 653: 344–355

    CAS  Google Scholar 

  84. Sidwell RW, Huffman JH, Coombs J, et al. A comparison of pyrimidinone analog immunomodulators for treatment of phlebovirus infections in mice. Antiviral Chem Chemother 1990; 1: 241–8

    CAS  Google Scholar 

  85. Krawczynski K. Hepatitis type E: enterically transmitted (epidemic) non-A, non-B hepatitis. In: McIntyre N, et al., editors. Oxford textbook of clinical hepatology. Oxford: Oxford University Press, 1991: 617–20

    Google Scholar 

  86. Hoofnagle JH. Interferon therapy of viral hepatitis. In: Baron S, et al., editors. Interferon: principles and medical applications. Galveston: University of Texas Medical Branch at Galveston, 1992: 433–62

    Google Scholar 

  87. Levin S, Hahn T. Interferon system in acute viral hepatitis. Lancet 1982; 1: 592

    PubMed  CAS  Google Scholar 

  88. Tassapoulos NC, Hadziyannis SJ, Wright GE. Recombinant human interferon alfa-2b in the management of acute type B hepatitis. Hepatology 1989; 10: 576

    Google Scholar 

  89. Iwarson S, Norkrans G, Nordenfelt E, et al. Interferon treatment in acute hepatitis B infection with prolonged course. Scand J Infect Dis 1980; 12: 233

    PubMed  CAS  Google Scholar 

  90. Sanchez-Tapias JM, Mas A, Bruguera M, et al. Recombinant alpha-2c interferon therapy in fulminant viral hepatitis. J Hepatol 1987; 5: 205

    PubMed  CAS  Google Scholar 

  91. Alexander GJM, Brahm J, Fagan EA, et al. Loss of HBsAg with interferon therapy in chronic hepatitis B virus infection. Lancet 1987; 1: 66

    Google Scholar 

  92. Thomas HC, Dusheiko GM, Lok ASF, et al. Comparative study of three doses of interferon alpha-2a in chronic active hepatitis B. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. New York: Williams and Wilkins, 1990: 1641–2

    Google Scholar 

  93. Hoofnagle JH, Peters MG, Mullen KD, et al. Randomized controlled trial of a four-month course of recombinant human alpha interferon in chronic type B hepatitis. Gastroenterology 1988; 95: 1318

    PubMed  CAS  Google Scholar 

  94. Di Bisceglie AM, Bergasa N, Fong T-L, et al. A randomized controlled trial of recombinant alpha interferon therapy for chronic hepatitis B. Hepatology 1991; 14: 70A

    Google Scholar 

  95. Perrillo RP, Schiff ER, Davis GL, et al. A randomized controlled trial of interferon alfa-2b alone and after prednisone withdrawal for the treatment of chronic hepatitis B. N Engl J Med 1990; 323: 295

    PubMed  CAS  Google Scholar 

  96. Wong DKH, Cheung AM, O’Rourke K, et al. Effect of alpha interferon treatment in patients with hepatitis B e-antigenpositive chronic hepatitis B. Ann Int Med 1993; 119: 312–323

    PubMed  CAS  Google Scholar 

  97. Omata M, Yokosuka O, Takano S, et al. Resolution of acute hepatitis C after therapy with natural beta interferon. Lancet 1991; 338: 914

    PubMed  CAS  Google Scholar 

  98. Alberti A, Chemello L, Benvegnu L, et al. Pilot study of interferon alpha-2a therapy in preventing chronic evolution of acute hepatitis C. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. New York: Williams and Wilkins, 1991: 656–8

    Google Scholar 

  99. Viladomiu L, Gonzalez A, Lopez-Talavera JC, et al. A randomized controlled trial of alpha-interferon in acute posttransfusion C hepatitis. J Hepatology 1990; 11: S64.58

    Google Scholar 

  100. Hoofnagle JH, Mullen KD, Jones DB, et al. Treatment of chronic non-A, non-B hepatitis with recombinant human alpha interferon: a preliminary report. N Engl J Med 1987; 315: 1575

    Google Scholar 

  101. Jacyna MR, Brooks MG, Loke RHT, et al. Randomised controlled trial of interferon alfa (lymphoblastoid interferon) in chronic non-A, non-B hepatitis. Br Med J 1989; 298: 80–2

    CAS  Google Scholar 

  102. Davis GL, Balart LA, Schiff ER, et al. Treatment of chronic hepatitis C with recombinant interferon alfa: a multicenter randomized, controlled trial. N Engl J Med 1989; 321: 1501

    PubMed  CAS  Google Scholar 

  103. Di Bisceglie AM, Martin P, Kassianides C, et al. Recombinant interferon alfa therapy for chronic hepatitis C: a randomized, double-blind, placebo-controlled trial. N Engl J Med 1989; 321: 1506

    PubMed  Google Scholar 

  104. Marcellin P, Boyer N, Giostra E, et al. Recombinant human alpha-interferon in patients with chronic non-A, non-B hepatitis: a multicenter randomized controlled trial from France. Hepatology 1991; 13: 393

    PubMed  CAS  Google Scholar 

  105. Saracco G, Rosina F, Torrani Cerenzia MR, et al. A randomized controlled trial of interferon alfa-2b as therapy for chronic non-A, non-B hepatitis. J Hepatology 1990; 11: S43

    Google Scholar 

  106. Ferenci P, Vogel W, Pristautz H, et al. One-year treatment of chronic non-A, non-B hepatitis with interferon alfa-2b. J Hepatology 1990; 11: S50

    Google Scholar 

  107. Weiland O, Schvarcz R, Wejstal R, et al. Therapy of chronic post-transfusion non-A, non-B hepatitis with interferon alfa-2b: Swedish experience. J Hepatology 1990; 11: S57

    Google Scholar 

  108. Gomez-Rubio M, Porres JC, Castillo I, et al. Prolonged treatment (18 months) of chronic hepatitis C with recombinant alpha-interferon in comparison with a control group. J. Hepatology 1990; 11: S63

    Google Scholar 

  109. Realdi G, Diaodata G, Bonetti P, et al. Recombinant human interferon alfa-2a in community-aquired non-A, non-B chronic active hepatitis: preliminary results of a randomized, controlled trial. J Hepatology 1990; 11: S68

    Google Scholar 

  110. Causse X, Godinot H, Chevallier M, et al. Comparison of 1 or 3 MU of interferon alfa-2b and placebo in patients with chronic non-A, non-B hepatitis. Gastronenterology 1991; 101: 497

    CAS  Google Scholar 

  111. Papo T, Marcellin P, Bernuau J, et al. Autoimmune chronic hepatitis excerbated by alpha-interferon. Ann Intern Med 1992; 116: 51

    PubMed  CAS  Google Scholar 

  112. Lindsay KL, Davis GL, Bodenheimer HC, et al. Predictors of relapse and response to re-treatment in patients with an initial response to recombinant alpha interferon (rIFN) therapy for chronic hepatitis C. Hepatology 1990; 12: 847

    Google Scholar 

  113. Reichard O, Andersson J, Schvarcz R, et al. Ribavirin treatment for chronic hepatitis C. Lancet 1991; 337: 1058

    PubMed  CAS  Google Scholar 

  114. Capra F, Casaril M, Gabrielli GB, et al. Alpha-interferon in the treatment of chronic viral hepatitis — effects on fibrogenesis serum markers. J Hepatol 1993; 18: 112–8

    PubMed  CAS  Google Scholar 

  115. Thomas HC, Farci P, Shein R, et al. Inhibition of hepatitis delta virus replication by lymphoblastoid human alpha interferon. Prog Clin Biol Res 1987; 234: 277

    PubMed  CAS  Google Scholar 

  116. Di Bisceglie AM, Martin P, Lisker-Melman M, et al. Therapy of chronic delta hepatitis with interferon alfa-2b. J Hepatol 1990; 11: S151

    PubMed  Google Scholar 

  117. Rosina F, Saracco G, Lattore V, et al. Treatment of chronic delta hepatitis with alpha 2 recombinant interferon. Prog Clin Biol Res 1987; 234: 299

    PubMed  CAS  Google Scholar 

  118. Rosina F, Rizzetto M. Treatment of chronic type D (delta) hepatitis with alpha interferon. Semin Liver Dis 1989; 9: 264

    PubMed  CAS  Google Scholar 

  119. Farci P, Mandas A, Lai CE, et al. Randomized controlled trial of high and low doses of interferon (IFN) alpha-2a (Roferon-A) in chronic HDV hepatitis: an interim report. In: Hollinger FB, Lemon SM, Margolis HS, editors. Viral hepatitis and liver disease. New York: Williams and Wilkins, 1991: 672–3

    Google Scholar 

  120. Greenberg SB. Clinical use of interferons in respiratory and other viral diseases. In Baron S, et al., editors. Interferon: principles and medical applications. Galveston: University of Texas Medical Branch at Galveston, 1992; 463–74

    Google Scholar 

  121. Negoro Y, Imanishi J, Matsuo A, et al. Treatment of epidemic keratoconjunctivitis by human leukocyte interferon. Jpn J Ophthalmol 1980; 24: 125–9

    Google Scholar 

  122. Romano A, Ladizensky E, Guarari-Rotman D, et al. Clinical effet of human-fibroblast-derived (beta) interferon in treatment of adenovirus epidemic keratoconjunctivitis and its complication. Metab Pediatr Syst Ophthalmol 1983: 7: 31–5

    PubMed  CAS  Google Scholar 

  123. Sundmacher R, Wigard, Cantell K. The value of exogenous interferon in adenovirus keratoconjunctivitis. Graefes Arch Clin Exp Ophthalmol 1982; 218: 139–45

    PubMed  CAS  Google Scholar 

  124. Chou S, Dylewski JS, Gaynon MW, et al. Alpha-interferon administration in cytomegalovirus retinitis. Antimicrob Agents Chemother 1984; 25: 25

    PubMed  CAS  Google Scholar 

  125. Stansfield SK, de la Pena W, Koenig S, et al. Human leukocyte interferon in the treatment and prophylaxis of acute hemorrhagic conjunctivitis. J Infect Dis 1984; 149: 822

    PubMed  CAS  Google Scholar 

  126. Emodi G, O’Reilly R, Muller A, et al. Effect of human exogenous leukocyte interferon in cytomegalovirus infections. J Infect Dis 1976; 133: 199

    Google Scholar 

  127. Wade JC, McGuffin RW, Springmeyer SC, et al. Treatment of cytomegaloviral pneumonia with high-dose acyclovir and human leukocyte interferon. J Infect Dis 1983; 148: 557

    PubMed  CAS  Google Scholar 

  128. Meyers JD, McGuffin RW, Byerson YJ, et al. Treatment of cytomegalovirus pneumonia after marrow transplant with combined vidarabine and human leukocyte interferon. J Infect Dis 1982; 146: 80

    PubMed  CAS  Google Scholar 

  129. Cheeseman SH, Rubin RH, Stewart JA, et al. Controlled clinical trial of prophylactic human-leukocyte interferon in renal transplantation. Effect of cytomegalovirus and herpes simplex virus infection. N Engl J Med 1979; 300: 1345

    PubMed  CAS  Google Scholar 

  130. Hirsch MS, Schooley RT, Cosimi AB, et al. Effects of interferon-alpha on cytomegalovirus reactivation syndromes in renal transplant recipients. N Engl J Med 1983; 308: 1489

    PubMed  CAS  Google Scholar 

  131. Weimar W, Kramer P, Bijnen AB, et al. The incidence of cytomegalo- and herpes simplex-virus infections in renal allograft recipients treated with high dose recombinant leucocyte interferon: a controlled study. Scand J Urol Nephrol Suppl. 1985; 92: 37

    PubMed  CAS  Google Scholar 

  132. Sundmacher R, Cantell K, Haug P, et al. Role of debridement and interferon in the treatment of dendritic keratitis. Graefes Arch Clin Exp Ophthalmol 1978; 207: 77–81

    CAS  Google Scholar 

  133. Sundmacher R, Cantell K, Haug P, et al. Interferon prophylaxis of dendritic keratitis recurrence during local steroid therapy. Ber Zusammenkunft Dtsch Ophthalmol Ges 1978; 75: 344–8

    PubMed  Google Scholar 

  134. De Konig EWJ, van Bijsterveld OP, Cantell K. Combination therapy for dendritic keratitis with acyclovir and α-interferon. Arch Ophthalmol 1983; 101: 1866–74

    Google Scholar 

  135. Meurs PJ, van Bkjsterveld OP. Combination therapy of recombinant human alpha 2 interferon and acyclovir in the treatment of herpes simplex keratitis. Antiviral Res 1985; 1 (Suppl.): 225

    PubMed  Google Scholar 

  136. Vannini A, Cembrano S, Assetto V, et al. Interferon-β treatment of herpes simplex keratitis. Ophthalmologica 1986; 192: 610

    Google Scholar 

  137. Ikic D, Prazic M, Smerdel S, et al. Therapy of herpetic gingivostomatitis in children with human leukocytic interferon. In: Ikic D, editor. Proc Symp Clin Use Interferon; Zagreb: Yugoslavian Acad Sci Arts, 1975: 203–6

    Google Scholar 

  138. Pazin GJ, Armstrong JA, Lam MT, et al. Prevention of reactivated herpes simplex infection by human leukocyte interferon after operation on the trigeminal root. N Engl J Med 1979; 301: 225

    PubMed  CAS  Google Scholar 

  139. Koskiniemi ML, Vaheri A, Valtonen S, et al. Trial with human leukocyte interferon and vidarabine in herpes simplex virus encephalitis: diagnostic and therapeutic problems. Acta Med Scand 1982; 668 (Suppl): 150

    CAS  Google Scholar 

  140. Ikic D, Smerdel S, Rajninger-Miholic R, et al. Treatment of labial and genital herpes with human leukocyte interferon. In: Ikic D, editor. Proc Symp Clin Use Interferon; Zagreb: Yugoslavian Acad Sci Arts, 1975: 195–99

    Google Scholar 

  141. Friedman-Kien AE, Klein RJ, Glaser RD, et al. Treatment of recurrent genital herpes with topical alpha interferon gel combined with nonoxynol 9. J Am Acad Dermatol 1986; 15: 989–96

    PubMed  CAS  Google Scholar 

  142. Kuhls TL, Sacher J, Pineda E, et al. Suppression of recurrent genital herpes simplex virus infection with recombinant α2 interferon. J Infect Dis 1986; 154: 437

    PubMed  CAS  Google Scholar 

  143. Emodi G, Askenazy J, Suemeghy Z. Preliminary results on tolerance and toxicity tests using human fibroblast interferon (beta-type) in patients with herpes genitalis infections. Int J Clin Pharmacol Res 1983; 3: 275

    Google Scholar 

  144. Mendelson J, Clecner BYA, Eiley S. Effect of recombinant interferon alpha 2 on clinical course of first episode genital herpes infection and subsequent recurrences. Genitourin Med 1986; 62: 97

    PubMed  CAS  Google Scholar 

  145. De Clercq E, Edy VG, De Vlieger H, et al. Intrathecal administration of interferon in neonatal herpes. J Pediatr 1975; 86: 736

    PubMed  Google Scholar 

  146. Eron LJ, Harvey L, Toy C, et al. Interferon in the prevention of genital herpes recurrence. Antimicrob Agents Chemother 1986; 30: 608–10

    PubMed  CAS  Google Scholar 

  147. Arvin AM, Kushner JH, Feldman S, et al. Human leukocyte interferon for the treatment of varicella in children with cancer. N Engl J Med 1982; 306: 761

    PubMed  CAS  Google Scholar 

  148. Merigan TC, Gallagher JG, Pollard RB, et al. Short-course human leukocyte interferon in treatment of herpes zoster in patients with cancer. Antimicrob Agents Chemother 1981; 19: 913

    Google Scholar 

  149. Heidemann E, Dietz K, Obert HJ, et al. Gunstingerer verlauf des herpes zoster bei immunosupprimierten patienten unter behandlung mit fibroblasteninterferon. Onkologie 1984; 7: 210

    PubMed  CAS  Google Scholar 

  150. Reunanen M, Ilonen J, Cantell K, et al. Treatment of an SSPE case undergoing a sudden relapse after a ten-year remission. Acta Neurol Scand 1978; 57 (67 Suppl.): 239

    Google Scholar 

  151. Risk WS, Haddad FS. The variable natural history of subacute sclerosing panencephalitis: a study of 118 cases from the Middle East. Arch Neurol 1979; 36: 610

    PubMed  CAS  Google Scholar 

  152. Old LJ. Tumor necrosis factor. In: Bonavida B, Granger B, editors. TNF: structure, mechanism of action, role in disease and therapy. New York: Karger, 1990: 130

    Google Scholar 

  153. Neta R, Openheim JJ, Durum SK. The cytokine concept: historical perspectives and current status of the cloned cytokines. In: Cohen S, editor. Lymphokines and the immune response. Boca Raton: CRC Press, 1990: 29–41

    Google Scholar 

  154. Wong GHW, Kamb A, Goeddel DV. Antiviral properties of TNF. In: Beutler B, editor. Tumor necrosis factors: the molecules and their emerging role in medicine. New York: Raven Press, 1990: 371–81

    Google Scholar 

  155. Wong GHW, Goeddel DV. Tumour necrosis factors α and β inhibit virus replication and synergize with interferons. Nature 1986; 323: 819–22

    PubMed  CAS  Google Scholar 

  156. Mestan J, Digel W, Mittnacht S, et al. Antiviral effects of recombinant tumour necrosis factor in vitro. Nature 1986; 323: 816–8

    PubMed  CAS  Google Scholar 

  157. Ito M, O’Malley JA. Antiviral effects of recombinant human tumor necrosis factor. Lymphokine Res 1987; 6: 309–18

    PubMed  CAS  Google Scholar 

  158. Ruggiero V, Antonelli G, Gentile M, et al. Comparative study on the antiviral activity of tumor necrosis factor (TNF)-α, lyymphotoxin/TNF-β, and IL-1 in WISH cells. Immunol Lett 1989; 21: 165–70

    PubMed  CAS  Google Scholar 

  159. Arakawa T, Hsu Y, Toth E, Stebbing N. The antiviral activity of recombinant human tumor necrosis factor-α. J Interferon Res 1987; 7: 103–5

    PubMed  CAS  Google Scholar 

  160. Kohase M, Henriksen-DeStefano D, May LT, et al. Induction of β2-interferon by tumor necrosis factor-α homeostatic mechanism in the control of cell proliferation. Cell 1986; 45: 659–66

    PubMed  CAS  Google Scholar 

  161. Ruggiero V, Antonelli G, Conciatori G, et al. The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells mediated by IFN-α induction. Antiviral Res 1989; 11: 77–88

    PubMed  CAS  Google Scholar 

  162. Goeddel DV, Aggarwal BB, Gray PW, et al. Tumor necrosis factors: gene structure and biological activities. Cold Spring Harbor Symp Quant Biol 1986; 51: 597–609

    PubMed  CAS  Google Scholar 

  163. Manogue KR, Van Deventer SJH, Cerami A. Tumour necrosis factor alpha or cachectin. In: Thomson A, editor. The cytokine handbook. New York: Academic Press, 1991: 241–56

    Google Scholar 

  164. Neta R, Sayers T, Oppenheim JJ. Relationship of tumor necrosis factor to interleukins. In: Vilcek J, Aggarwal B, editors. Tumor necrosis factor. New York: Marcel Dekker, 1991: 29–41

    Google Scholar 

  165. Samuel CE. Interferon induction of the antiviral state: proteins induced by interferons and their possible roles in the antiviral mechanisms of interferon action. In: Pfeffer LM, editor. Mechanisms of interferon actions. Boca Raton: CRC Press, 1987: 111–30

    Google Scholar 

  166. Aderka D, Novick D, Hahn T, et al. Increase of vulnerability to lymphotoxin in cells infected by vesicular stomatitis virus and its further augmentation by interferon. Cell Immunol 1985; 92: 218–25

    PubMed  CAS  Google Scholar 

  167. Koff WC, Fann AV. Human tumor necrosis factor-α kills herpesvirus-infected but not normal cells. Lymphokine Res 1986; 5: 215–21

    PubMed  CAS  Google Scholar 

  168. Lorence RM, Rood PA, Kelly KW. Newcastle disease virus as an antineoplastic agent: induction of tumor necrosis factor-α and augmentation of its cytotoxicity. J Natl Cancer Inst 1988; 80: 1305–12

    PubMed  CAS  Google Scholar 

  169. Imanishi J, Ike H, Yamada A. Inhibitory effect of interferons and tumor necrosis factor on syncytium formation by bovine leukemia virus. C R Soc Seances Soc Biol Fil 1987; 181: 722–6

    CAS  Google Scholar 

  170. Matsuyama T, Hamamoto Y, Soma G, et al. Cytocidal effect of tumor necrosis factor on cells chronically infected with immunodeficiency virus (HIV): enhancement of HIV replication. J Virol 1989; 63: 2504–9

    PubMed  CAS  Google Scholar 

  171. Folks TM, Clouse KA, Justement J, et al. Tumor necrosis factor α induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc Natl Acad Sci USA 1989; 86: 2365–8

    PubMed  CAS  Google Scholar 

  172. Collins T, Lapierre LA, Fiers W, et al. 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 USA 1986; 83: 446–50

    PubMed  CAS  Google Scholar 

  173. Lidbury BA, Aston R, Ramshaw IA, et al. The enhancement of human tumor necrosis factor-α antiviral activity in vivo by monoclonal and specific polyclonal antibodies. Lymphokine Cytokine Res 1993; 12: 69–74

    PubMed  CAS  Google Scholar 

  174. Warren RS, Starnes HF Jr, Gabrilove JL, et al. The acute metabolic effects of tumour necrosis factor administration in humans. Arch Surg 1987; 122: 1396–1403

    PubMed  CAS  Google Scholar 

  175. Ruddle NH, Turetskaya RL. Tumor necrosis factor β. In: Thomson A, editor. The cytokine handbook. New York: Academic Press, 1991: 257–67

    Google Scholar 

  176. Sastry KJ, Reddy RHR, Pandito R, et al. HIV-1 tat gene induces tumor necrosis factor-β (lymphotoxin) in a human Blymphoblastoid cell line. J Biol Chem 1990; 265: 20091–3

    PubMed  CAS  Google Scholar 

  177. Bielefeldt Ohmann H, Babiuk LA. Influence of interferons α11 and γ and of tumour necrosis factor on persistent infection with bovine viral diarrhoea virus in vitro. J Gen Virol 1988; 69: 1399–1403

    PubMed  Google Scholar 

  178. Anderson KP, Lie YS, Low ML, et al. Effects of tumor necrosis factor-α treatment on mortality in murine cytomegalovirus-infected mice. Antiviral Res 1993; 21: 343–55

    PubMed  CAS  Google Scholar 

  179. Schmitt DA, Sasaki H, Pollard RB, et al. Antiviral effects of recombinant human tumor necrosis factor-α in combination with natural interferon-β in mice infected with herpes simplex virus type 1. Antiviral Res 1992; 19: 347–52

    PubMed  CAS  Google Scholar 

  180. Garland JM. Colony stimulating factors. In: Thomson A, editor. The cytokine handbook. New York: Academic Press, 1991: 269–300

    Google Scholar 

  181. Roilides E, Pizzo PA. Modulation of host defenses by cytokines: evolving adjuncts in prevention and treatment of serious infections in immuno-compromised hosts. Clin Infect Dis 1992; 15: 508–24

    PubMed  CAS  Google Scholar 

  182. Groopman J, Mitsuyasu RT, DeLeo MJ, et al. Effect of recombinant human granulocyte-macrophage colony stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 1987; 317: 593–8

    PubMed  CAS  Google Scholar 

  183. Kaplan SS, Zdziarski UE, Basford RE, et al. Effect of in vivo recombinant human granulocyte-macrophage colony stimulating factor on peripheral blood granulocyte function. Clin Res 1988; 36: 566A

    Google Scholar 

  184. Hammer SM, Gillis JM, Pinkston P, et al. Effect of zidovudine and granulocyte-macrophage colony stimulating factor on human immunodeficiency virus replication in alveolar macrophages. Blood 1990; 75: 1215–9

    PubMed  CAS  Google Scholar 

  185. Hammer SM, Gillis JM, Groopman JE, Rose RM. In vitro modification of human immunodeficiency virus infection by granulocyte-macrophage colony stimulating factor and gamma interferon. Proc Natl Acad Sci USA 1986; 83: 8734–6

    PubMed  CAS  Google Scholar 

  186. DeNoon DJ. GM-CSF. In: Directory of antiviral and immunomodulatory therapies for AIDS. Atlanta: CDC AIDS Weekly, 1990: 75–8

    Google Scholar 

  187. Perno CF, Yarchoan R, Cooney DA, et al. Replication of human immunodeficiency virus in monocytes: granocyte/macrophage colony stimulating factor (GM-CSF) potentiates viral production yet enhances the antiviral effect mediated by 3′-azido-3′-deoxythymidine (AZT) and other nucleoside congeners of thymidine. J Exp Med 1989; 169: 933–5

    PubMed  CAS  Google Scholar 

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  1. Institute for Antiviral Research, Department of Biology and the Center for Persons with Disabilities, Utah State University, Logan, Utah, 84322-6895, USA

    Reed P. Warren & Robert W. Sidwell

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Warren, R.P., Sidwell, R.W. The Potential Role of Cytokines in the Treatment of Viral Infections. Clin. Immunother. 1, 15–30 (1994). https://doi.org/10.1007/BF03258488

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