Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2012 Oct 30;42(5):749–765. doi: 10.2165/00003495-199142050-00003

The Use of Interferon-α in Virus Infections

N B Finter 1,, S Chapman 2, P Dowd 1, J M Johnston 2, V Manna 1, N Sarantis 1, N Sheron 4, G Scott 3, S Phua 5, P B Tatum 2
PMCID: PMC7100942  PMID: 1723372

Summary

The interferons (IFN) act too slowly to arrest acute viral infections, but interferon-α (IFNα) preparations have proved useful in some chronic infections and will clearly be used increasingly in these in the future.

In the preparations derived from human leucocytes or cultured B lymphoblastoid cells, which are in routine clinical use, mixtures of a number of distinct subtypes of human IFNα have been identified. There are also 3 slightly different verrions of the same single subtype, IFNα-2, made by recombinant DNA procedures in bacteria.

IFNα preparations are injected intramuscularly or subcutaneously. Dose-related side effects are common but usually tolerable, but prolonged treatment may cause increasing fatigue and depression. Some patients form neutralising antibodies which block the effects of the IFN; these appear to be relatively more common after recombinant IFNα-2 than after IFN derived from human cells.

Given intranasally, IFTα can prevent a subsequent experimental rhinovirus infection, or the spread of natural colds within a family. Repeated administration progressively damages the nasal mucosa, so that long term prophylaxis is not possible.

IFNα has proved useful in patients with papillomavirus warts of the larynx, ano-genital region (condyloma acuminata) and skin (common warts). Treatment regimens remain to be optimised and are likely to include surgery or other treatments.

IFNα and zidovudine (azidothymidine) synergistically inhibit the growth of HIV in vitro, and combination are on trial in patients with early AIDS. Very large doses of IFNα are effective against Kaposi’s sarcoma in some AIDS patients.

In chronic hepatitis B, continuing virus replication may lead to cirrhosis or primary liver cancer. Earlier clinical trials with IFNα gave inconclusive results, but recent large studies have confirmed that 25 to 40% of patients obtain benefit; this probably results from both the antiviral and the immunomodulatory effects of IFNα.

In patients with chronic hepatitis C, the biochemical markers usually improve rapidly during IFNα administration, but relapse if treatment is stopped after only a few months; to increase the chances of sustained cure, the treatment period is now being prolonged.

Keywords: Human Immunodeficiency Virus, Interferon, Chronic Hepatitis, Genital Wart, Condyloma Acuminata

References

  1. Alberti I, Fattovich G, Pontisso P, et al. Interferon treatment of antiHBe positive and HBV DNA positive chronic hepatitis B. Chemoterapia. 1988;7(3):15–19. [PubMed] [Google Scholar]
  2. Aldershvile J, Dietrichson A, Skinhoj P, et al. and the Copenhagen Hepatitis Acute Programme. Chronic persistent hepatitis: serological classification and meaning of the hepatitis B e system. Hepatology. 1982;2:243–246. doi: 10.1002/hep.1840020209. [DOI] [PubMed] [Google Scholar]
  3. Alexander G.J.M, Brahm J, Fagan E.A, et al. Loss of HBsAg with interferon therapy in chronic HBV infection. Lancet. 1987;2:66–69. doi: 10.1016/S0140-6736(87)92735-8. [DOI] [PubMed] [Google Scholar]
  4. Anderson M.G, Harrison T.J, Alexander G, et al. Randomised controlled trial of lymphoblastoid interferon for chronic active hepatitis. Gut. 1987;28:619–622. doi: 10.1136/gut.28.5.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andres L.L, Sawhney V.K, Scullard G.H, et al. Dane particle DNA polymerase and HBeAg: impact on clinical, laboratory and histological findings in hepatitis B-associated chronic liver disease. Hepatology. 1981;1:583–585. doi: 10.1002/hep.1840010604. [DOI] [PubMed] [Google Scholar]
  6. Antonelli G, Currenti M, Turriziani O, et al. Neutralizing antibodies to interferon-α: relative frequency in patients treated with different interferon preparations. Journal of Infectious Diseases. 1991;163:882–885. doi: 10.1093/infdis/163.4.882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Aoki F.Y, Crawley J.C.W. Distribution and removal of human serum albumin-technetium 99M instilled intranasally by drops and spray. British Journal of Clinical Pharmacology. 1976;3:869–878. doi: 10.1111/j.1365-2125.1976.tb00640.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Baron G, Ashmen M, Fischl M, et al. Immunomodulation of patients with AIDS related complexes (ARC) during therapy with recombinant interferon gamma (IFNG). Fourth International Conference on AIDS, Stockholm. Abstract no. 3510, 1988
  9. Baron S, Isaacs A. Absence of interferon in lungs from fatal cases of influenza. British Medical Journal. 1962;1:18–20. doi: 10.1136/bmj.1.5270.18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Beasley R.P, Hwang L.Y, et al. Epidemiology of hepatocellular carcinoma. In: Vyas G.N, et al., editors. Viral hepatitis and liver disease. Orlando: Grune and Stratton; 1984. pp. 209–224. [Google Scholar]
  11. Berman B, Davis-Reed L, Silverstein L, et al. Treatment of Verrucae Vulgaris with α2interferon. Journal of Infectious Diseases. 1986;154:328–330. doi: 10.1093/infdis/154.2.328. [DOI] [PubMed] [Google Scholar]
  12. Billiau A. The main concepts and achievements in interferon research: a historical account. In: Billiau A, editor. Interferon 1, general and applied aspects. Amsterdam: Elsevier; 1984. pp. 22–58. [Google Scholar]
  13. Borucki MJ, Von Roenn JH, Williams RN, Pollard RB. A multicentre open-label study of subcutaneously administered recombinant interferon beta (rIFN beta) in patients at risk for progression to AIDS. Sixth International Conference on AIDS, San Francisco. Abstract no. SB463, 1990
  14. Bratzke B, Stadler R, Tiel H, et al. Combination of interferon (r alpha 2) and zidovudine for therapy of HIV-associated Kaposi’s sarcoma (KS). Fourth International Conference on AIDS, Stockholm, Abstract no. 3631, 1988
  15. Buimovici-Klein E, Lange M, Klein R.J, et al. Long term follow up of serum interferon and its acid stability in a group of homosexual men. AIDS Research. 1986;2:99–108. doi: 10.1089/aid.1.1986.2.99. [DOI] [PubMed] [Google Scholar]
  16. Casato M, Laganà B, Bonomo L, et al. Clinical effects of interferons in essential mixed cryoglobulinemia. In: Indiveri F, et al., editors. Proceedings of the First International Symposium on Biological Response Modifiers, San Remo, November 1989. Bologna: Esculapio; 1990. pp. 49–54. [Google Scholar]
  17. Chu C.M, Karayiannis P, Fowler M.J, et al. Natural history of chronic hepatitis B virus infection in Taiwan; studies of hepatitis B virus DNA in serum. Hepatology. 1985;5:431–434. doi: 10.1002/hep.1840050315. [DOI] [PubMed] [Google Scholar]
  18. Chuang T.-Y, Perry H.O, Kurland L.T, Ilstrup K.M. Condyloma acuminatum in Rochester, Minn., 1950–1978. Archives of Dermatology. 1984;120:469–475. doi: 10.1001/archderm.1984.01650400051012. [DOI] [PubMed] [Google Scholar]
  19. Condylomata International Collaborative Study Group Recurrent condylomata acuminata treated with recombinant interferon alfa-2a. Journal of the American Medical Association. 1991;265:2684–2687. doi: 10.1001/jama.1991.03460200064036. [DOI] [PubMed] [Google Scholar]
  20. Crespi M. The effect of interferon on cells persistently infected with HIV AIDS. 1989;3:33–36. [PubMed] [Google Scholar]
  21. Davis G.L, Balart L.A, Schiff E.R, et al. Treatment of chronic hepatitis C with recombinant interferon alpha. New England Journal of Medicine. 1989;321:1501–1505. doi: 10.1056/NEJM198911303212203. [DOI] [PubMed] [Google Scholar]
  22. De Stefano E, Friedman R.M, Friedman-Kien A.E, et al. Acid-labile human leucocyte interferon in homosexual men with Kaposi’s sarcoma and lymphadenopathy. Journal of Infectious Diseases. 1982;146:451–455. doi: 10.1093/infdis/146.4.451. [DOI] [PubMed] [Google Scholar]
  23. Department of HealthSocial Security Sexually transmitted diseases. Genitourinary Medicine. 1985;61:204–207. doi: 10.1136/sti.61.3.204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Desmyter J, De Groote J, Desmet V.J, et al. Administration of human fibroblast interferon in chronic hepatitis B infection. Lancet. 1976;2:645–647. doi: 10.1016/S0140-6736(76)92460-0. [DOI] [PubMed] [Google Scholar]
  25. Di Bischelie A.M, Martin P, Kassianides C, et al. Recombinant interferon alpha therapy for chronic hepatitis C: a randomised double-blind placebo-controlled trial. New England Journal of Medicine. 1989;321:1506–1510. doi: 10.1056/NEJM198911303212204. [DOI] [PubMed] [Google Scholar]
  26. Douglas R.B, Moore B.W, Miles H.B, et al. Prophylactic efficacy of intranasal alpha2interferon against rhinovirus infections in the family setting. New England Journal of Medicine. 1986;314:65–70. doi: 10.1056/NEJM198601093140201. [DOI] [PubMed] [Google Scholar]
  27. Dusheiko G.M, Paterson A.C, Pitcher L, et al. Recombinant leucocyte interferon treatment of chronic hepatitis B: an analysis of two therapeutic trials. Journal of Hepatology. 1986;3(2):S199–S207. doi: 10.1016/S0168-8278(86)80121-0. [DOI] [PubMed] [Google Scholar]
  28. de Wit R, Schattenkerk J.C.M, Boucher C.A.B, et al. Clinical and virological effects of high dose recombinant interferon-alpha in disseminated AIDS related Kaposi’s sarcoma. Lancet. 1988;2:1214–1217. doi: 10.1016/S0140-6736(88)90810-0. [DOI] [PubMed] [Google Scholar]
  29. de Wit R, Schattenkerk K.M.E, Boucher C.A.B, et al. Clinical and virological effects of high dose recombinant interferon alpha in disseminated AIDS-related Kaposi’s sarcoma. Lancet. 1988;2:1214–1217. doi: 10.1016/S0140-6736(88)90810-0. [DOI] [PubMed] [Google Scholar]
  30. Eron L.J, Judson F, Tucker S, et al. Interferon therapy for condylomata acuminata. New England Journal of Medicine. 1986;315:1059–1064. doi: 10.1056/NEJM198610233151704. [DOI] [PubMed] [Google Scholar]
  31. Eskelinen A, Mashkilleyson N. Optimum treatment of genital warts. Drugs. 1987;34:599–603. doi: 10.2165/00003495-198734050-00006. [DOI] [PubMed] [Google Scholar]
  32. Eyster M.E, Goedert J.J, Poon M.-C, Preble O.T. Acid labile alpha interferon. New England Journal of Medicine. 1983;309:583–586. doi: 10.1056/NEJM198309083091003. [DOI] [PubMed] [Google Scholar]
  33. Finter N.B, Fantes K.H, Lockyer M.J, et al. The DNA content of crude and purified human lymphoblastoid (Namalwa cell) interferon prepared by Wellcome Biotechnology Limited. In: Hopps H.E, Petricciani J.C, et al., editors. Abnormal cells, new products and risks. Gaithersburg MD: Tissue Culture Association; 1985. pp. 125–128. [Google Scholar]
  34. Finter N.B, Fantes K.H. The purity and safety of interferons prepared for clinical use: the case for lymphoblastoid interferon. In: Gresser I, editor. Interferon 2. London: Academic Press; 1980. pp. 65–79. [Google Scholar]
  35. Finter NB. Why are there so many subtypes of alpha-interferons? Journal of Interferon Research, Special Issue, pp. 185-194, 1991
  36. Fischl M.A, Uttamchandani R.B, Resnick L, et al. A phase 1 study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi’s sarcoma. Journal of Acquired Immunodeficiency Syndrome. 1991;4:1–10. [PubMed] [Google Scholar]
  37. Foster G.R, Goldin R.D, Ackrill A.M, Kerr I.M, Thomas H.C, et al. Hepatitis B Pol gene product inhibits the cellular response to interferon. Journal of Interferon Research. 1990;10(1):S15. [Google Scholar]
  38. Freund M, von Wussow P, Diedrich H, et al. Recombinant human interferon (IFN) alpha-2b in chronic myelogenous leukaemia: dose dependency of response and frequency of neutralising anti-interferon antibodies. British Journal of Haematology. 1989;172:350–356. doi: 10.1111/j.1365-2141.1989.tb07715.x. [DOI] [PubMed] [Google Scholar]
  39. Friedman-Kein A.E, Eron L.J, Conant M, et al. Natural interferon alpha for treatment of condylomata acuminata. Journal of the American Medical Association. 1988;259:533–538. doi: 10.1001/jama.1988.03720040025021. [DOI] [PubMed] [Google Scholar]
  40. Gall S.A, Hughes C.E, Mounts P, et al. Efficacy of human lymphoblastoid interferon in the therapy of resistant condyloma acuminata. Obstetrics and Gynaecology. 1986;67:643–651. doi: 10.1097/00006250-198605000-00008. [DOI] [PubMed] [Google Scholar]
  41. Gall S.A, Hughes C.E, Trofatter K. Interferon for the therapy of condyloma acuminatum. American Journal of Obstetrics and Gynaecology. 1985;153:157–163. doi: 10.1016/0002-9378(85)90103-6. [DOI] [PubMed] [Google Scholar]
  42. Geffen J.R. Klein RJ, Friedman-Klein AE. Intralesional administration of large doses of human leukocyte interferon for the treatment of condylomata acuminata. Journal of Infectious Diseases. 1984;150:612–615. doi: 10.1093/infdis/150.4.612. [DOI] [PubMed] [Google Scholar]
  43. Gibson J.R, Harvey S.G, Kemmett D, et al. Treatment of common and plantar viral warts with human lymphoblastoid interferon-α: pilot studies with intralesional, intramuscular and dermojet injections. British Journal of Dermatology. 1984;115(31):76–79. doi: 10.1111/j.1365-2133.1986.tb02113.x. [DOI] [PubMed] [Google Scholar]
  44. Gibson J.R. Intralesional lymphoblastoid interferon alpha for the treatment of cutaneous, non-genital viral warts. Archives of Dermatology. 1986;122:1098–1099. doi: 10.1001/archderm.1986.01660220012003. [DOI] [PubMed] [Google Scholar]
  45. Gibson J.R. The treatment of viral warts with interferons. Journal of Antimicrobial Chemotherapy. 1988;21:391–393. doi: 10.1093/jac/21.4.391. [DOI] [PubMed] [Google Scholar]
  46. Gobel U, Arnold W, Wahn V, et al. Comparison of human fibroblast and leukocyte interferon in the treatment of severe laryngeal papillomatosis in children. European Journal of Paediatrics. 1981;137:175–176. doi: 10.1007/BF00441312. [DOI] [PubMed] [Google Scholar]
  47. Goeddel D.V, Yelverton E, Ullrich A, et al. Human leukocyte interferon produced by E. coli is biologically active. Nature (London) 1980;287:411–416. doi: 10.1038/287411a0. [DOI] [PubMed] [Google Scholar]
  48. Goepfert H, Sessions R, Gutterman J, et al. Leukocyte interferon in patients with juvenile laryngeal papillomatosis. Annals of Otology, Rhinology and Laryngology. 1982;91:431–436. doi: 10.1177/000348948209100422. [DOI] [PubMed] [Google Scholar]
  49. Greenberg H.B, Pollard R, Lutwick L, et al. Effect of human leukocyte interferon on hepatitis B virus infection in patients with chronic active hepatitis. New England Journal of Medicine. 1976;295:517–522. doi: 10.1056/NEJM197609022951001. [DOI] [PubMed] [Google Scholar]
  50. Gresser I, Tovey M.G, Bandu T.M, et al. Role of interferon in the pathogenesis of virus diseases as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomy-ocarditis virus infection. Journal of Experimental Medicine. 1976;144:1305–1315. doi: 10.1084/jem.144.5.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Gresser I, Tovey M.G, Maury C, Bandu M.T. Role of interferon in the pathogenesis of virus diseases as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease and influenza viruses. Journal of Experimental Medicine. 1976;144:1316–1323. doi: 10.1084/jem.144.5.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Gugliotta L, Catani L, Vianelli N, et al. Efficacy of interferon alpha-2a treatment in essential thrombocythaemia. Journal of Interferon Research. 1989;9(2):S112. [Google Scholar]
  53. Gustavo G-C, Lovet C, Navarro-Carrola E, et al. Survival of 30 patients with AIDS related Kaposi’s sarcoma treated with AZT and alpha 2a interferon. Sixth International Conference on AIDS, San Francisco. Abstract no. SB515, 1990
  54. Hadziyannis S.J, Lieberman H.M, Karvountzis G.G, et al. Analysis of liver disease, nuclear HBcAg, viral replication and hepatitis B virus DNA in liver and serum of HBeAg vs anti-HBe positive carriers of hepatitis B virus. Hepatology. 1983;5:656–662. doi: 10.1002/hep.1840030505. [DOI] [PubMed] [Google Scholar]
  55. Haglund S, Lundquist P, Cantell K, et al. Interferon therapy in juvenile laryngeal papillomatosis. Archives of Otolaryngology, Head and Neck Surgery. 1981;197:327–332. doi: 10.1001/archotol.1981.00790420001001. [DOI] [PubMed] [Google Scholar]
  56. Haller O, Arnheiter H, Lindenmann J, Gresser I. Host gene influences sensitivity to interferon action selectively for influenza virus. Nature (London) 1980;283:660–662. doi: 10.1038/283660a0. [DOI] [PubMed] [Google Scholar]
  57. Hartshorn K.L, Neumeyer D, Vogt M.W, et al. Activity of Interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro. AIDS Research and Human Retroviruses. 1987;3:125–133. doi: 10.1089/aid.1987.3.125. [DOI] [PubMed] [Google Scholar]
  58. Hartshorn K.L, Vogt M.W, Chou T.C, et al. Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha-A interferon. Antimicrobial Agents and Chemotherapy. 1987;31:168–172. doi: 10.1128/AAC.31.2.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Hatch K.D. Evaluation of interferon alpha-2 in the treatment of condyloma acuminatum. Journal of Reproduction Physiology. 1986;31:979. [Google Scholar]
  60. Hayden F.G, Albrecht J.K, Kaiser D.L, Gwaltney J.M. Prevention of natural colds by contact: prophylaxis with intranasal alpha2-interferon. New England Journal of Medicine. 1986;314:71–75. doi: 10.1056/NEJM198601093140202. [DOI] [PubMed] [Google Scholar]
  61. Hayden F.G, Gwaltney J.M., Jr Intranasal interferon-alpha2 for prevention of rhinovirus infection and illness. Journal of Infectious Diseases. 1983;148:543–550. doi: 10.1093/infdis/148.3.543. [DOI] [PubMed] [Google Scholar]
  62. Hayden F.G, Gwaltney J.M., Jr Intranasal interferon-alphaatreatment of experimental rhinoviral colds. Journal of Infectious Diseases. 1984;150:174–180. doi: 10.1093/infdis/150.2.174. [DOI] [PubMed] [Google Scholar]
  63. Hayden F.G, Mills S.E, Johns M.E. Human tolerance and histopathologic effects of long term administration of intranasal interferon-alpha2. Journal of Infectious Diseases. 1983;148:914–921. doi: 10.1093/infdis/148.5.914. [DOI] [PubMed] [Google Scholar]
  64. Hayden F.G, Winther B, Donowitz G, et al. Human nasal mucosal responses to topically applied recombinant leukocyte A interferon. Journal of Infectious Diseases. 1987;156:64–72. doi: 10.1093/infdis/156.1.64. [DOI] [PubMed] [Google Scholar]
  65. Healy G.B, Gelber R.D, Trowbridge A.L, et al. Treatment of recurrent respiratory papillomatosis with human leukocyte interferon. New England Journal of Medicine. 1988;319:401–407. doi: 10.1056/NEJM198808183190704. [DOI] [PubMed] [Google Scholar]
  66. Henle W. Interference phenomena between animal viruses: a review. Journal of Immunology. 1950;91:203–236. [PubMed] [Google Scholar]
  67. Higgins P.G, Al-Nakib W, Barrow G.I, Tyrrell D.A.J. Recombinant human interferon-gamma as prophylaxis against rhinovirus colds in volunteers. Journal of Interferon Research. 1988;8:591–596. doi: 10.1089/jir.1988.8.591. [DOI] [PubMed] [Google Scholar]
  68. Higgins P.G, Al-Nakib W, Willman J, Tyrrell D.A.J. Interferon-beta ser as prophylaxis against experimental rhinovirus infection in volunteers. Journal of Interferon Research. 1986;6:153–159. doi: 10.1089/jir.1986.6.153. [DOI] [PubMed] [Google Scholar]
  69. Higgins P.G, Philipotts R.J, Scott G.M, et al. Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers. Antimicrobial Agents and Chemotherapy. 1983;24:713–715. doi: 10.1128/AAC.24.5.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Ho D.D, Hartshorn K.L, Rota T.R, et al. Recombinant human interferon alpha-A suppresses HTLV-III replication in vitro. Lancet. 1985;1:602–604. doi: 10.1016/S0140-6736(85)92144-0. [DOI] [PubMed] [Google Scholar]
  71. Hoofnagle J.H, Dusheiko G.M, Seef L.B, et al. Seroconversion from hepatitis B e antigen to antibody in chronic type B hepatitis. Annals of Internal Medicine. 1981;94:744–748. doi: 10.7326/0003-4819-94-6-744. [DOI] [PubMed] [Google Scholar]
  72. Hoofnagle J.H, Peters M, Mullen K.D, et al. Randomized controlled trial of recombinant interferon in patients with chronic hepatitis B. Gastroenterology. 1988;95:1318–1325. doi: 10.1016/0016-5085(88)90367-8. [DOI] [PubMed] [Google Scholar]
  73. Hoofnagle J.H. Chronic hepatitis. Editorial. New England Journal of Medicine. 1990;323:337–339. doi: 10.1056/NEJM199008023230510. [DOI] [PubMed] [Google Scholar]
  74. Hovanessian A.G. The double stranded RNA-activated protein kinase induced by interferon: ds RNA-PK. Journal of Interferon Research. 1989;9:641–647. doi: 10.1089/jir.1989.9.641. [DOI] [PubMed] [Google Scholar]
  75. Hsu H.C, Su I.J, Lai M.Y, et al. Biologic and prognostic significance of hepatocyte hepatitis B core antigen expression in the natural course of chronic hepatitis B virus. Journal of Hepatology. 1987;5:45–50. doi: 10.1016/S0168-8278(87)80060-0. [DOI] [PubMed] [Google Scholar]
  76. Hull R, McGeoch D.J. Some highlights of virus research in 1988. Journal of General Virology. 1989;70:2825–2842. doi: 10.1099/0022-1317-70-11-2825. [DOI] [PubMed] [Google Scholar]
  77. Idéo G, Bellati G, Pedraglio E, Leandro G. One year of therapy of non A, non B/C chronic hepatitis with recombinant α-2a interferon (r-IFN) or lymphoblastoid α interferon (1-IFN). Abstracts of the 25th Meeting of the European Association for the Study of Liver Disease. Journal of Hepatology. 1990;11(2):S31. doi: 10.1016/0168-8278(90)91458-9. [DOI] [Google Scholar]
  78. Ikić D, Bosnić N, Smerdel S, et al. Double-blind clinical study with human leukocyte interferon in therapy of condylomata acuminata. Proceedings of the Symposium on Clinical Use of Interferon, Yugoslav Academy of Sciences and Arts, Zagreb, pp. 229-233, 1975
  79. Interferon Alpha Study Group A randomised placebo-controlled trial of recombinant human interferon alpha 2a in patients with AIDS. Journal of Acquired Immune Deficiency Syndrome. 1988;1:111–118. [PubMed] [Google Scholar]
  80. Isaacs A, Lindenmann J. Virus interference 1. The Interferon. Proceedings of the Royal Society Series B 147, pp. 258-267, 1957 [DOI] [PubMed]
  81. Jacyna M.R, Brooks M.G, Loke R.H.T, et al. Randomised controlled trial of interferon alpha (lymphoblastoid) in chronic non-A, non-B hepatitis. British Medical Journal. 1989;289:80–82. doi: 10.1136/bmj.298.6666.80. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Johnston M.D. Sources of interferon for clinical use: alpha-interferons from human lymphoblastoid cells. In: Finter N.B, Oldham R.K, editors. Interferon 4: in vivo and clinical studies. Amsterdam: Elsevier; 1985. pp. 81–87. [Google Scholar]
  83. Kashima H, Leventhal B, Clark K, et al. Interferon alpha-N1 (Wellferon) in juvenile onset recurrent respiratory papillomatosis: results of randomised study in twelve collaborative institutions. Laryngoscope. 1988;98:334–340. doi: 10.1288/00005537-198803000-00020. [DOI] [PubMed] [Google Scholar]
  84. Kirby P, Wells D, Kiviat N, Corey L. Phase I trial of intramuscular recombinant human gamma interferon for refractory genital warts. Journal of Investigative Dermatology. 1986;86:485. [Google Scholar]
  85. Kojima S, Futatski T, Hatano Y, Koide T. Purification and characterisation of human interferon-alpha subtypes from Namalwa lymphoblastoid cells. Journal of Interferon Research. 1989;9(2):S178. [Google Scholar]
  86. Kornbluth R.S, Oh P.S, Munis J.R, et al. Interferons and bacterial lipopolysaccharide protect macrophages from productive infection by human immunodeficiency virus in vitro. Journal of Experimental Medicine. 1989;169:1137–1151. doi: 10.1084/jem.169.3.1137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Kovacs J.A, Deyton L, Davey V, et al. Combined zidovudine and interferon-alpha therapy in patients with Kaposi sarcoma and the acquired immunodeficiency syndrome (AIDS) Annals of Internal Medicine. 1989;111:280–287. doi: 10.7326/0003-4819-111-4-280. [DOI] [PubMed] [Google Scholar]
  88. Krown S.E, Gold J.W.M, Niedzwiecki D, et al. Interferon-alpha with zidovudine: safety, tolerance, and clinical and virologic effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS) Annals of Internal Medicine. 1990;112:812–821. doi: 10.7326/0003-4819-112-11-812. [DOI] [PubMed] [Google Scholar]
  89. Krown SE, Paredes J, Bundow D, Flomenberg N. Combination therapy with interferon-alpha, zidovudine and recombinant granulocyte-macrophage colony stimulating factor (GM-CSF): a phase 1 trial in patients with AIDS associated Kaposi’s sarcoma. Sixth International Conference on AIDS, San Francisco. Abstract no. SB513, 1990b
  90. Lai C.L, Lok A.S, Lin H.J, et al. Placebo controlled trial of recombinant alpha interferon in Chinese HBsAg carrier children. Lancet. 1987;2:877–880. doi: 10.1016/S0140-6736(87)91371-7. [DOI] [PubMed] [Google Scholar]
  91. Lane H.C, Davey V, Kovacs J.A, et al. Interferon alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. Annals of Internal Medicine. 1990;112:805–811. doi: 10.7326/0003-4819-112-11-805. [DOI] [PubMed] [Google Scholar]
  92. Leventhal B.G, Kashima H.K, Weck P.W, et al. Randomised surgical adjuvant trial of interferon alpha-N1 in recurrent papillomatosis. Archives of Otolaryngology, Head and Neck Surgery. 1988;114:1163–1169. doi: 10.1001/archotol.1988.01860220097032. [DOI] [PubMed] [Google Scholar]
  93. Liaw L.F, Lin S.M, Sheen I.S. Treatment of chronic type B hepatitis in South East Asia. American Journal of Medicine. 1988;85(2A):147–149. [PubMed] [Google Scholar]
  94. Liaw Y.F, Chu C.M, Chen T, et al. Clinical and histological events preceding hepatitis B e antigen seroconversion in chronic type B hepatitis. Gastroenterology. 1983;84:216–219. [PubMed] [Google Scholar]
  95. Lindh G, Weiland O, Svedmyr A, et al. Long term follow-up of 60 patients with chronic hepatitis B. I. Seroconversion in the hepatitis B e-system, frequency of delta infection and histological outcome. Liver. 1986;6:7–12. doi: 10.1111/j.1600-0676.1986.tb00261.x. [DOI] [PubMed] [Google Scholar]
  96. Lok ASF, Lai CL. Incidence, neutralizing activity and clinical significance of interferon antibodies in chronic hepatitis B patients receiving recombinant α-interferons. In Hollinger FB, et al. (Eds) Viral hepatitis and liver disease, in press, 1991
  97. Lok A.S.F, Lai C.-L, Leung E.-Y. Interferon antibodies may negate the antiviral effects of recombinant α-interferon treatment in patients with chronic hepatitis B infection. Hepatology. 1990;12:1266–1270. doi: 10.1002/hep.1840120603. [DOI] [PubMed] [Google Scholar]
  98. McCabe B, Clark K. Interferon and laryngeal papillomatosis: the Iowa experience. Annals of Otology, Rhinology and Laryngology. 1983;92:2–7. doi: 10.1177/000348948309200102. [DOI] [PubMed] [Google Scholar]
  99. McDonald J.A, Caruso L, Karayiannis P, Scully L, Harris J.R, et al. Diminished responsiveness of male homosexual chronic hepatitis B carriers with HTLV-III antibodies to recombinant alpha-interferon. Hepatology. 1987;7:719–723. doi: 10.1002/hep.1840070417. [DOI] [PubMed] [Google Scholar]
  100. Miles S.A, Wang H, Cortes E, et al. Beta-interferon therapy in patients with poor prognosis Kaposi sarcoma related to the acquired immunodeficiency syndrome (AIDS) Annals of Internal Medicine. 1990;112:582–589. doi: 10.7326/0003-4819-112-8-582. [DOI] [PubMed] [Google Scholar]
  101. Nagata S, Taira H, Hall A, et al. Synthesis in E. coli of a polypeptide with human leucocyte interferon activity. Nature (London) 1980;284:316–320. doi: 10.1038/284316a0. [DOI] [PubMed] [Google Scholar]
  102. Niimura M. Intralesional human fibroblast interferon in common warts. Journal of Dermatology (Tokyo) 1983;10:217–220. doi: 10.1111/j.1346-8138.1983.tb01130.x. [DOI] [PubMed] [Google Scholar]
  103. Oettgen H.F, Real F.X, Krown S.E. Treatment of AIDS associated Kaposi’s sarcoma with recombinant alpha interferon. Immunobiology. 1986;172:269–274. doi: 10.1016/S0171-2985(86)80108-5. [DOI] [PubMed] [Google Scholar]
  104. Oon C.J. Hepatitis B virus (HBV): the challenges ahead. Annals of the Academy of Medicine (Singapore) 1988;17:257–260. [PubMed] [Google Scholar]
  105. Orholm M, Pedersen C, Mathiesen L, et al. Suppression of p24 antigen in sera from HIV-infected individuals with low dose alpha-interferon and zidovudine: a pilot study. AIDS. 1989;3:97–100. doi: 10.1097/00002030-198902000-00008. [DOI] [PubMed] [Google Scholar]
  106. Pennington J.E, Groopman J.E, Small G.J, et al. Effect of intravenous recombinant gamma interferon on the respiratory burst of blood monocytes from patients with AIDS. Journal of Infectious Diseases. 1986;153:609–612. doi: 10.1093/infdis/153.3.609. [DOI] [PubMed] [Google Scholar]
  107. Perillo R.B, Schiff E.R, Davis G.L, et al. A randomized controlled trial of interferon alpha-2b alone and after prednisolone withdrawal for the treatment of chronic hepatitis B. New England Journal of Medicine. 1990;323:295–301. doi: 10.1056/NEJM199008023230503. [DOI] [PubMed] [Google Scholar]
  108. Perrillo R.P, Regenstein F.G, Peters M.G, De Schryver-Kecskemeti K, Bodicky C.J, et al. Prednisolone withdrawal followed by recombinant alpha-interferon in the treatment of chronic type B hepatitis. Annals of Internal Medicine. 1988;109:95–100. doi: 10.7326/0003-4819-109-2-95. [DOI] [PubMed] [Google Scholar]
  109. Pestka S, Langer J.A, Zoon K.C, Samuel C.E. Interferons and their actions. Annual Review of Biochemistry. 1987;56:727–777. doi: 10.1146/annurev.bi.56.070187.003455. [DOI] [PubMed] [Google Scholar]
  110. Petersen C.S, Bjerring P, Larsen J, Blaakaer J, Hagdrup H, et al. Systemic interferon alpha-2b increases the cure rate in laser treated patients with multiple persistent genital warts: a placebo-controlled study. Genitourinary Medicine. 1991;67:99–102. doi: 10.1136/sti.67.2.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  111. Philipotts R.J, Higgins P.G, Willman J.S, et al. Intranasal lymphoblastoid interferon (Wellferon) prophylaxis against rhinovirus and influenza virus in volunteers. Journal of Interferon Research. 1984;4:535–541. doi: 10.1089/jir.1984.4.535. [DOI] [PubMed] [Google Scholar]
  112. Philipotts R.J, Scott G.M, Higgins P.G, et al. An effective dose regimen for prophylaxis against rhinovirus infection by intranasal administration of interferon-alpha2. Antiviral Research. 1983;3:121–136. doi: 10.1016/0166-3542(83)90034-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Poli G, Orenstein J.M, Kinter A, et al. Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines. Science. 1989;244:575–577. doi: 10.1126/science.2470148. [DOI] [PubMed] [Google Scholar]
  114. Realdi G, Alberti A, Rugge M, et al. Seroconversion from hepatitis B e antigen to anti-HBe in chronic hepatitis B virus infection. Gastroenterology. 1980;79:195–199. [PubMed] [Google Scholar]
  115. Reichman RC, Farchione A, Whitley R, et al. Placebo-controlled trials of three different interferon preparations administered parenterally for condyloma acuminata. Abstract S1430. 28th Intersciences Conference on Antimicrobial Agents and Chemotherapy, Los Angeles, California, October 23, p. 26, 1988
  116. Renault P.F, Hoofnagle J.H, Park Y, et al. Psychiatric complications of long term interferon alpha therapy. Archives of Internal Medicine. 1987;147:1577–1580. doi: 10.1001/archinte.1987.00370090055011. [DOI] [PubMed] [Google Scholar]
  117. Samo T.C, Greenberg S.B, Couch R.B, et al. Efficacy and tolerance of intranasally applied recombinant leukocyte A interferon in normal volunteers. Journal of Infectious Diseases. 1983;148:535–542. doi: 10.1093/infdis/148.3.535. [DOI] [PubMed] [Google Scholar]
  118. Samo T.C, Greenberg S.B, Palmer J.M, et al. Intranasally applied recombinant leukocyte A interferon in normal volunteers. II. Determination of the minimal effective and tolerable dose. Journal of Infectious Diseases. 1984;150:181–188. doi: 10.1093/infdis/150.2.181. [DOI] [PubMed] [Google Scholar]
  119. Sanchez-Tapias J.M, Vilar J.H, Costa J, et al. Natural history of chronic persistent hepatits B: relationship between hepatitis B virus replication and the course of the disease. Journal of Hepatology. 1984;1:15–27. doi: 10.1016/S0168-8278(85)80064-7. [DOI] [PubMed] [Google Scholar]
  120. Scott G.M, Onwubalili J.K, Robinson J.A, et al. Tolerance of one month intranasal interferon. Journal of Medical Virology. 1985;17:99–106. doi: 10.1002/jmv.1890170202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Scott G.M, Phillpotts R.J, Wallace J, et al. Purified interferon as protection against rhinovirus infection. British Medical Journal. 1982;284:1822–1825. doi: 10.1136/bmj.284.6332.1822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Scott G.M, Tyrrell D.A.J. Antiviral effects of interferon in man. In: Finter N.B, Oldham R.K, editors. Interferon 4 in vivo and clinical studies. Amsterdam: Elsevier; 1985. pp. 181–215. [Google Scholar]
  123. Scott G, Csonka G. Effect of injections of small doses of human fibroblast interferon into genital warts: a pilot study. British Journal of Venereal Diseases. 1979;55:442–445. doi: 10.1136/sti.55.6.442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Scully L.J, Shein R, Karayiannis P, et al. Lymphoblastoid interferon therapy of chronic HBV infection: a comparison of 12 vs 24 weeks of thrice weekly treatment. Journal of Hepatology. 1987;5:51–58. doi: 10.1016/S0168-8278(87)80061-2. [DOI] [PubMed] [Google Scholar]
  125. Steis R.G, Smith J.W, Erber W.J, et al. Resistance to recombinant interferon alpha 2a in hairy cell leukaemia associated with neutralising anti-interferon antibodies. New England Journal of Medicine. 1988;318:1409–1413. doi: 10.1056/NEJM198806023182201. [DOI] [PubMed] [Google Scholar]
  126. Strander H, Cantell K. Production of interferon by human leucocytes in vitro. Annales Medicinae Experimentalis et Biologiae Fennae. 1966;44:265–273. [PubMed] [Google Scholar]
  127. Thompson B.J, Doran M, Lever A.M.L, et al. Alpha interferon therapy for non-A, non-B hepatitis transmitted by gammaglobulin replacement therapy. Lancet. 1987;1:539–541. doi: 10.1016/S0140-6736(87)90178-4. [DOI] [PubMed] [Google Scholar]
  128. Thurmond LM, Brand CM, Leventhal BG, Finter NB, Johnston JM. Antibodies in recurrent respiratory papillomatosis patients treated with lymphoblastoid interferon. Journal of Laboratory and Clinical Medicine, in press, 1991 [PubMed]
  129. Vadhan-Raj S, Wong G, Gnecco C, et al. Immunological variables as predictors of prognosis in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome. Cancer Research. 1986;46:417–425. [PubMed] [Google Scholar]
  130. Vance J.C, Bart B.J, Hansen R.C, et al. Intralesional recombinant alpha-2 interferon for the treatment of patients with condyloma acuminatum or verruca plantaris. Archives of Dermatology. 1986;122:272–277. doi: 10.1001/archderm.1986.01660150050014. [DOI] [PubMed] [Google Scholar]
  131. Vogt M.W, Durno A.G, Chou T.-C, et al. Synergistic interaction of 2′, 3′-dideoxycytidine and recombinant interferon-alpha-A on replication of human immunodeficiency virus type 1. Journal of Infectious Diseases. 1988;158:378–385. doi: 10.1093/infdis/158.2.378. [DOI] [PubMed] [Google Scholar]
  132. Volberding P.A, Mitsuyasu R.T, Golando J.P, et al. Treatment of Kaposi’s sarcoma with interferon alpha-2b (Intron A) Cancer. 1987;59:620–627. doi: 10.1002/1097-0142(19870201)59:3+<620::AID-CNCR2820591309>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  133. von Wussow P, Hartman F, Freund M, et al. Leukocyte-derived interferon-alpha in patients with antibodies to recombinant IFM-alpha 2b. Lancet. 1988;1:882–883. doi: 10.1016/S0140-6736(88)91628-5. [DOI] [PubMed] [Google Scholar]
  134. von Wussow P, Jakschies D, Freund M, et al. Treatment of anti rIFN-alpha 2 antibody positive CML patients with natural interferon-alpha. Journal of Interferon Research. 1989;9(2):S113. [Google Scholar]
  135. Weck PK, Leventhal BG, Brand C, et al. Detection and incidence of neutralising antibodies to Interferon-alpha-n1. Journal of Interferon Research (Suppl. 1): S37-S43, 1989 [PubMed]
  136. Weck P, Trofatter K.F, Reichman R.C, et al. Interferon alpha-N1 (Wellferon) in severe recurrent genital warts: report of a multistudy program. In: Schellekens H, Cantell K, et al., editors. Biology of the interferon system. Amsterdam: Elsevier; 1986. pp. 485–491. [Google Scholar]
  137. Weitz G, Bekisz J, Zoon K, Arnheiter H. Purification and characterization of a human Mx protein. Journal of Interferon Research. 1989;9:679–689. doi: 10.1089/jir.1989.9.679. [DOI] [PubMed] [Google Scholar]
  138. Williams G.T, Colby C.B. Recombinant human interferon-beta suppresses the replication of HIV and acts synergistically with AZT. Journal of Interferon Research. 1989;9:709–718. doi: 10.1089/jir.1989.9.709. [DOI] [PubMed] [Google Scholar]
  139. Yamada O, Hattori N, Kurimura T, et al. Inhibition of growth of HIV by human natural interferon in vitro. AIDS Research on Human Retroviruses. 1988;4:287–294. doi: 10.1089/aid.1988.4.287. [DOI] [PubMed] [Google Scholar]
  140. Yamamoto J.K, Barre-Sinoussi F, Bolton V, et al. Human alpha- and beta-interferon but not gamma- supresses the in vitro replication of LAV, HTLV and ARV-2. Journal of Interferon Research. 1986;6:143–152. doi: 10.1089/jir.1986.6.143. [DOI] [PubMed] [Google Scholar]
  141. Yokosuka O, Omata M, Imazeki F, et al. Changes of hepatitis B virus DNA in liver and serum caused by recombinant leukocyte interferon treatment: analysis of intrahepatic replicative hepatitis B virus DNA. Hepatology. 1985;5:728–734. doi: 10.1002/hep.1840050505. [DOI] [PubMed] [Google Scholar]
  142. Zoon K.C, Miller D, Bekisz J, et al. Chemical characterisation of human lymphoblastoid interferon-alpha species. Journal of Interferon Research. 1989;9(2):S184. [Google Scholar]

Articles from Drugs are provided here courtesy of Nature Publishing Group

RESOURCES