Biologic Response Modifiers (Interleukins and Interferons)

  • Gwendolyn Anne Fyfe
  • H. Clifford Lane


The first cases of AIDS were described in 1981 and the virus was initially isolated in 1983. Since that time, substantial progress has been made in the prophylaxis and treatment of the opportunistic infections associated with HIV-related immune deficiency and some progress has been made in controlling the persistent viral replication which characterizes HIV infection. Unfortunately, no antiretroviral drug or combination of drugs has yet resulted in complete and lasting suppression of HIV replication and damage and depletion of the immune system continues. Furthermore, the rapid development of antiretroviral resistance limits the utility of even current combination regimens. While the continued development of new antiretroviral agents without overlapping patterns of resistance provides some hope that the progression of HIV disease may be controlled ultimately by a multidrug approach, such as has been successful in tuberculosis, this remains a hypothesis.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Acquire Immune Deficiency Syndrome Acquire Immunodeficiency Syndrome Natural Killer Activity 


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  1. Baron, S., Tyring, S. K., Fleischmann, W. R., Coppenhaver, D. H., Niesel, D. W., Klimpel, G. R., Stanton, G. J., and Hughes, T. K., 1991, The interferons. Mechanisms of action and clinical applications. J. Am. Med. Assoc. 266:1375–1383.CrossRefGoogle Scholar
  2. Bell, S. J. D., Cooper, D. A., Kemp, B. E., Doherty, R. R., and Penny, R., 1992, Heterogeneous effects of exogenous IL-2 on HIV-specific cell-mediated immunity (CMI), Clin. Exp. Immunol 90:6–12.PubMedCrossRefGoogle Scholar
  3. Benedetto, N., Auriault, C., Darcy, F., Lando, D., Watier, H., and Capron, A., 1991, Effect of rIFN-γ and IL-2 treatments in mouse and nude rat infections with Toxoplasma gondii, Eur. Cytokine Network 2:107–114.Google Scholar
  4. Berglund, O., Engman, K., Ehrnst, A., Andersson, J., Lidman, K., Åkerlund, B., Sönnerborg, A., and Strannegård, Ö., 1991, combined treatment of symptomatic human immunodeficiency virus type 1 infection with native interferon-alpha and zidovudine, J. Infect. Dis. 163:710–715.PubMedCrossRefGoogle Scholar
  5. Biron, C. A., and Gazzinelli, R. T., 1995, Effects of IL-12 on immune responses to microbial infections: A key mediator in regulating disease outcome, Curr. Opin. Immunol. 7:485–496.PubMedCrossRefGoogle Scholar
  6. Bonavida, B., Katz, J., and Gottlieb, M., 1986, Mechanisms of defective NK cell activity in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. I. Defective trigger on NK cells for NKCF production by target cells and partial restoration by IL-2, J. Immunol. 137:1157–1163.PubMedGoogle Scholar
  7. Borrow, P., Lewicki, H., Hahn, B. H., Shaw, G. M., and Oldstone, M. B., 1994, Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection, J. Virol. 68:6103–6110.PubMedGoogle Scholar
  8. Chehimi, J., Starr, S. E., Frank, L., Rengaraju, M., Jackson, S. J., Lianes, C., Kobayashi, M., Perussia, B., Young, D., Nickbarg, E., Wolf, S. F., and Trinchieri, G., 1992, Natural killer (NK) cell stimulatory factor increases the cytotoxic activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients, J. Exp. Med. 175:789–796.PubMedCrossRefGoogle Scholar
  9. Chehimi, J., Starr, S. E., Frank, I., D’Andrea, A., Ma, X., MacGregor, R. R., Sennelier, J., and Trinchieri, G., 1994, Impaired interleukin 12 production in human immunodeficiency virus-infected patients, J. Exp. Med. 179:1361–1366.PubMedCrossRefGoogle Scholar
  10. Chouaib, S., Chehimi, J., Bani, L., Genetet, N., Tursz, T., Gay, F., Trinchieri, G., and Mami-Chouaib, F., 1994, Interleukin 12 induces the differentiation of major histocompatibility complex class I-primed cytotoxic T-lymphocyte precursors into allospecific cytotoxic effectors, Proc. Natl. Acad. Sci. USA 91:12659–12663.PubMedCrossRefGoogle Scholar
  11. Ciobanu, N., Weite, K., Kruger, G., Venuta, S., Gold, J., Feldman, S. P., Wang, C. Y., Koziner, B., Moore, M. A. S., Safai, B., and Mertelsmann, R., 1983, Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and its in vitro correction by interleukin 2, J. Clin. Immunol. 3:332–340.PubMedCrossRefGoogle Scholar
  12. Clark, S. J., Saag, M. S., Decker, W. D., Campbell-Hill, S., Roberson, J. L., Veldkamp P. J., Kappes, J. C., Hahn, B. H., and Shaw, G. M., 1991, High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection, N. Engl. J. Med. 324:954–960.PubMedCrossRefGoogle Scholar
  13. Clerici, M., and Shearer, G. M., 1993, A TH1-TH2 switch is a critical step in the etiology of HIV infection, Immunol. Today 14:107–111.PubMedCrossRefGoogle Scholar
  14. Clerici, M., Lucey, D. R., Berzofsky, J. A., Pinto, L. A., Wynn, T. A., Blatt, S. P., Dolan, M. J., Hendrix, C. W., Wolf, S., F., and Shearer, G. M., 1993a, Restoration of HIV-specific cell-mediated immune responses by interleukin-12 in vitro, Science 262:1721–1724.PubMedCrossRefGoogle Scholar
  15. Clerici, M., Hakim, F. T., Venzon, D. J., Blatt, S., Hendrix, C. W., Wynn, T. A., and Shearer, G. M., 1993b, Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus seropositive individuals, J. Clin. Invest. 91:759–765.PubMedCrossRefGoogle Scholar
  16. Cotran, R. S., Pober, J. S., Gimbrone, M. A., Jr., Springer, T. A., Wiebke, E. A., Gaspari, A. A., Rosenberg, S. A., and Lotze, M. T., 1987, Endothelial activation during interleukin 2 immunotherapy, J. Immunol. 139:1883–1888.Google Scholar
  17. Daar, E. S., Moudgil, T., Meyer, R. D., and Ho, D. D., 1991, Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection, N. Engl. J. Med. 324:961–964.PubMedCrossRefGoogle Scholar
  18. Davey, R. T., Jr., Wells, M. J., Piscitelli, S. C., Kovacs, J. A., Walker, R. E., Polis, M. A., Falloon, J., Masur, H., Metcalf, J. A., Fyfe, G. A., and Lane, H. C., 1994, Subcutaneous administration of interleukin-2 in HIV-1-infected individuals [abstract No. 278], Infectious Disease Society of America, Orlando, Florida, October 7–9, 1994. Google Scholar
  19. Deresinski, S. C., Israelski, D. I., Frascino, R. J., Joseph, P., Galpin, J. E., Conant, M. A., Resnick, L., Fyfe, G. A., Alexander, J. M., Moody, D., and Moseley, A., 1995, Randomized multi center comparison of treatment of HIV infected patients: Activated CD8+ cells plus rIL-2 plus antiretroviral (AR) therapy vs rIL2 plus AR therapy vs AR therapy alone [abstract No. 206], Abstracts of the 2nd National Conference on Human Retroviruses. Google Scholar
  20. deWit, R., Schattenkerk, J. K. M. E., Boucher, C. A. B., Bakker, P. J. M., Veenhof, K. H. N., and Danner, S. A., 1988, Clinical and virological effects of high-dose recombinant interferon-alpha in disseminated AIDS-related Kaposi’s sarcoma, Lancet 2:1214–1217.CrossRefGoogle Scholar
  21. Edlin, B. R., Weinstein, R. A., Whaling, S. M., Ou, C.-Y, Connolly, P. J., Moore, J. L., and Bitran, J. D., 1992, Zidovudine-interferon-alpha combination therapy in patients with advanced human immunodeficiency virus type 1 infection: Biphasic response of p24 antigen and quantitative polymerase chain reaction, J. Infect. Dis. 165:793–798.PubMedCrossRefGoogle Scholar
  22. Ernst, M., Kern, P., Flad, H.-D., and Ulmer, A. J., 1986, Effects of systemic in vivo interleukin-2 (IL-2) reconstitution in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) on phenotypes and functions of peripheral blood mononuclear cells (PBMC), J. Clin. Immunol. 6:170–181.PubMedCrossRefGoogle Scholar
  23. Falloon, J., Owen, C., Kovacs, J., Leavitt, R., Metcalf, J., and Lane, H. C., 1995, MK-639 (Merck HIV Protease Inhibitor) with interleukin-2 (IL2) in HIV [abstract No. 1176], 1CAAC Abstracts: 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco.Google Scholar
  24. Fei, P. C., Solmone, M., Viora, M., Vanacore, P., Pugliese, O., Giglio, A., Caprilli, F., and Ameglio, F., 1994, Apoptosis in HIV infection: Protective role of IL-2, J. Biol. Regul. Homeostat. Agents 8:60–64.Google Scholar
  25. Fischl, M. A., Uttamchandani, R. B., Resnick, L., Agarwal, R., Fletcher, M. A., Patrone-Reese, J., Dearmas, L., Chickekel, J., McCann, M., and Myers, M., 1991, A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alphanl and concomitant zidovudine in patients with AIDS-related Kaposi’s sarcoma, J. Acq. Immune Defic. Syndr. 4:1–10.Google Scholar
  26. Francis, M. L., Meltzer, M. S., and Gendelman, H. E., 1992, Interferons in the persistence, pathogenesis, and treatment of HIV infection, AIDS Res. Hum. Retrovir. 8:199–207.PubMedCrossRefGoogle Scholar
  27. Gazzinelli, R. T., Giese, N. A., and Morse, H. C., III, 1994, In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS), J. Exp. Med. 180:2199–2208.PubMedCrossRefGoogle Scholar
  28. Gelmann, E. P., Preble, O. T., Steis, R., Lane, H. C., Rook, A. H., Wesley, M., Jacob, J., Fauci, A., Masur, H., and Longo, D., 1985, Human lymphoblastoid interferon treatment of Kaposi’s sarcoma in the acquired immune deficiency syndrome. Clinical response and prognostic parameters, Am. J. Med. 78:737–741.PubMedCrossRefGoogle Scholar
  29. Graziosi, C., Pantaleo, G., Gantt, K. R., Forten, J.-R, Demarest, J. F., Cohen, O. J., Sekaly, R. P., and Fauci, A. S., 1994, Lack of evidence for the dichotomy of Th1 and Th2 predominance in HIV-infected individuals, Science 265:248–252.PubMedCrossRefGoogle Scholar
  30. Groopman, J. E., Gottlieb, M. S., Goodman, J., Mitsuyasu, R. T., Conant, M. A., Prince, H., Fahey, J. L., Derezin, M., Weinstein, W. M., Casavante, C., Rothman, J., Rudnick, S. A., and Volberding, P. A., 1984, Recombinant alpha-2 interferon therapy for Kaposi’s sarcoma associated with the acquired immunodeficiency syndrome, Ann. Intern. Med. 100:671–676.PubMedCrossRefGoogle Scholar
  31. Gupta, S., Gillis, S., Thornton, M., and Goldberg, M., 1984, Autologous mixed lymphocyte reaction in man. XIV. Deficiency of the autologous mixed lymphocyte reaction in acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC): In vitro effect of purified interleukin-1 and interleukin-2, Clin. Exp. Immunol. 58:395–401.PubMedGoogle Scholar
  32. Hartshorn, K., Neumeyer, D., Vogt, M., Schooley, R. T., and Hirsch, M. S., 1987, Activity of interferons alpha, beta, and gamma against human immunodeficiency virus replication in vitro, AIDS Res. Hum. Retrovir. 3:125–133.PubMedCrossRefGoogle Scholar
  33. Ho, D. D., Hartshorn, K. L., Rota, T. R., Andrews, C. A., Kaplan, J. C., Schooley, R. T., and Hirsch, M. S., 1985, Recombinant human interferon alfa-A suppresses HTLV-III replication in vitro, Lancet 1:602–604.PubMedCrossRefGoogle Scholar
  34. Ho, D. D., Neumann, A. IL, Perelson, A. S., Chen, W., Leonard, J. M., and Markowitz, M., 1995, Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection, Nature 373:123–126.PubMedCrossRefGoogle Scholar
  35. Jeevan, A., and Asherson, G. L., 1988, Recombinant interleukin-2 limits the replication of Mycobacterium lepraemurium and Mycobacterium bovis BCG in mice, Lymphokine Res. 7:129–140.PubMedGoogle Scholar
  36. Johnson, V. A., Barlow, M. A., Merrill, D. P., Chou, T.-C., and Hirsch, M. S., 1990, Three-drug synergistic inhibition of HIV-1 replication in vitro by zidovudine, recombinant soluble CD4, and recombinant interferon-alpha, J. Infect. Dis. 161:1059–1067.PubMedCrossRefGoogle Scholar
  37. Kern, P., Toy, J., and Dietrich, M., 1985, Preliminary clinical observations with recombinant interleukin-2 in patients with AIDS or LAS, Blut 50:1–6.PubMedCrossRefGoogle Scholar
  38. Koenig, S., Conley, A. J., Brewah, Y. A., Jones, G. M., Leath, S., Boots, L. J., Davey, V., Pantaleo, G., Demarest, J. E., Carter, C., Wannebo, C., Yannelli, J. R., Rosenberg, S. A., and Lane, H. C., 1995, Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression, Nature Med. 1:330–336.PubMedCrossRefGoogle Scholar
  39. Kovacs, J. A., Deyton, L., Davey, R., Falloon, J., Zunick, K., Lee, D., Metcalf, J. A., Bigley, J. W., Sawyer, L. A., Zoon, K. C., Masur, H., Fauci, A. S., and Lane, H. C., 1989, Combined zidovudine and interferonalpha therapy in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome (AIDS), Ann. Intern. Med. 111:280–287.PubMedCrossRefGoogle Scholar
  40. Kovacs, J. A., Baseler, M., Dewar, R. J., Vogel, S., Davey, R. T., Falloon, J., Polis, M. A., Walker, R. E., Stevens, R., Salzman, N. P., Metcalf, J. A., Masur, H., and Lane, H. C., 1995a, Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. A preliminary study, N. Engl. J. Med. 332:567–575.PubMedCrossRefGoogle Scholar
  41. Kovacs, J. A., Vogel, S., Albert, J., Falloon, J., Davey, R., Walker, R., Polis, M., Metcalf, J., Baseler, M., Foulkes, M., Fyfe, G., Masur, H., and Lane, H. C., 1995b, A randomized trial of intermittent interleukin-2 therapy in HIV-infected patients with CD4 counts >200 cells/mm3, Abstract presented at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, August.Google Scholar
  42. Krown, S. E., Gold, J. W. M., Niedzwiecki, D., Bundow, D., Flomenberg, N., Gansbacher, B., and Brew, B. J., 1990, Interferon-alpha with zidovudine: Safety, tolerance, and clinical and virologie effects in patients with Kaposi sarcoma associated with the acquired immunodeficiency syndrome (AIDS), Ann. Intern. Med. 112:812–821.PubMedCrossRefGoogle Scholar
  43. Lane, H. C., Siegel, J. P., Rook, A. H., Masur, H., Gelmann, E. P., Quinnan, G. V., and Fauci, A. S., 1984, Use of interleukin-2 in patients with acquired immunodeficiency syndrome, J. Biol. Response Modif. 3:512–516.Google Scholar
  44. Lane, H. C., Kovacs, J. A., Feinberg, J., Herpin, B., Davey, V., Walker, R., Deyton, L., Metcalf, J. A., Baseler, M., Salzman, N., Manischewitz, J., Quinnan, G., Masur, H., and Fauci, A. S., 1988, Anti-retroviral effects of interferon-alpha in AIDS-associated Karposi’s sarcoma, Lancet 2:1218–1222.PubMedCrossRefGoogle Scholar
  45. Lane, H. C., Davey, R. T., Sherwin, S. A., Masur, H., Rook, A. H., Manischewitz, J. F., Quinnan, G. V., Smith, P. D., Easter, M. E., and Fauci, A. S., 1989, Phase I trial of recombinant interferon-gamma in patients with Kaposi’s sarcoma and the acquired immunodeficiency syndrome (AIDS), J. Clin. Immunol. 9:351–361.PubMedCrossRefGoogle Scholar
  46. Lane, H. C., Davey, V., Kovacs, J. A., Feinberg, J., Metcalf, J. A., Herpin, B., Walker, R., Deyton, L., Davey, R. T., Falloon, J., Polis, M. A., Salzman, N. P., Baseler, M., Masur, H., and Fauci, A. S., 1990, Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial, Ann. Intern. Med. 112:805–811.PubMedCrossRefGoogle Scholar
  47. Lotze, M. T., Robb, R. J., Sharrow, S. O., Frana, L. W., and Rosenberg, S. A., 1984, Systemic administration of interleukin-2 in humans, J. Biol. Response Modif. 3:475–482.Google Scholar
  48. McElrath, M. J., Kaplan, G., Burkhardt, R. A., and Cohn, Z. A., 1990, Cutaneous response to recombinant interleukin 2 in human immunodeficiency virus 1-seropositive individuals, Proc. Natl. Acad. Sci. USA 87:5783–5787.PubMedCrossRefGoogle Scholar
  49. Mackall, C. L., Fleisher, T. A., Brown, M. R., Andrich, M. P., Chen, C. C., Feuerstein, I. M., Horowitz, M. E., Magrath, I. T., Shad, A. T., Steinberg, S. M., Wexler, L. H., and Gress, R. E., 1995, Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy, N. Engl. J. Med. 332:143–149.PubMedCrossRefGoogle Scholar
  50. McMahon, D. K., Armstrong, J. A., Huang, X. L., Rinaldo, C. R., Jr., Gupta, P., Whiteside, T. L., Pazin, G. J., Tripli, C., and Ho, M., 1994, A phase I study of subcutaneous recombinant interleukin-2 in patients with advanced HIV disease while on zidovudine, AIDS 8:59–66.PubMedCrossRefGoogle Scholar
  51. Maggi, E., Mazzetti, M., Ravina, A., Annunziato, F., De Carli, M., Piccinni, M. P., Manetti, R., Carbonari, M., Pesce, A. M., Del Prete, G., and Romagnani, S., 1994, Ability of HIV to promote a TH1 to TH0 shift and to replicate preferentially in TH2 and TH0 cells, Science 265:244–248.PubMedCrossRefGoogle Scholar
  52. Mazza, P., Bocchia, M., Tumietto, E., Costigliola, P., Coronado, O., Bandini, G., Conte, R., Ricchi, E., Vianelli, N., Raise, E., Fondacaro, A., Re, M. D., Vignoli, M., Chiodo, E., and Tura, S., 1992, Recombinant interleukin-2 (rIL-2) in acquired immune deficiency syndrome (AIDS): Preliminary report in patients with lymphoma associated with HIV infection, Eur. J. Haematol. 49:1–6.PubMedCrossRefGoogle Scholar
  53. Mertelsmann, R., Weite, K., Sternberg, C., O’Reilly, R., Moore, M. A. S., Clarkson, B. D., and Oettgen, H. R., 1984, Treatment of immunodeficiency with interleukin-2: Initial exploration, J. Biol. Response Modif. 4:483–490.Google Scholar
  54. Miles, S. A., Wang, H. J., Cortes, E., Carden, J., Marcus, S., and Mitsuyasu, R. T., 1990, 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. Intern. Med. 112:582–589.PubMedCrossRefGoogle Scholar
  55. Morgan, D. A., Ruscetti, F. W., and Gallo, R., 1976, Selective in vitro growth of T lymphocytes from normal bone marrows, Science 193:1007–1008.PubMedCrossRefGoogle Scholar
  56. Murray, H. W., Weite, K., Jacobs, J. L., Rubin, B. Y., Mertelsmann, R., and Roberts, R. B., 1985, Production of and in vitro response to interleukin 2 in the acquired immunodeficiency syndrome, J. Clin. Invest. 76:1959–1964.PubMedCrossRefGoogle Scholar
  57. Murray, H. W., DePamphilis, J., Schooley, R. T., and Hirsch, M. S., 1988, Circulating interferon gamma in AIDS patients treated with interleukin-2, N. Engl. J. Med. 318:1538–1539.PubMedCrossRefGoogle Scholar
  58. O’Brien, W A., Grovit-Ferbas, K., Namazi, A., Ovcak-Derzic, S., Wang, H.-J., Park, J., Yeramian, C., Mao, S.-H., and Zack, J. A., 1995, Human immunodeficiency virus-type 1 replication can be increased in peripheral blood of seropositive patients after influenza vaccination, Blood 86:1082–1089.PubMedGoogle Scholar
  59. Pantaleo, G., Demarest, J. R., Soudeyns, H., Graziosi, C., Denis, F., Adelsberger, J. W., Borrow, P., Saag, M. S., Shaw, G. M., Sekaly, R. P., and Fauci, A. S., 1994, Major expansion of CD8+ T cells with a predominant Vβ usage during the primary immune response to HIV, Nature 370:463–467.PubMedCrossRefGoogle Scholar
  60. Pitha, P. M., Wivel, N. A., Fernie, B. R., and Harper, H. P., 1979, Effect of interferon and murine leukaemia virus infection. IV. Formation of non-infectious virus in chronically infected cells, J. Gen. Virol. 42:467–480.PubMedCrossRefGoogle Scholar
  61. Poli, G., Orenstein, J. M., Kinter, A., Folks, T. M., and Fauci, A. S., 1989, Interferon-alpha but not AZT suppresses HIV expression in chronically infected cell lines, Science 244:575–577.PubMedCrossRefGoogle Scholar
  62. Ramachandran, R. V., Katzenstein, D., and Merigan, T. C., 1994, Long-term effects of interleukin-2 on CD4 cell counts in human immunodeficiency virus-infected patients, J. Infect Dis. 170:1044–1046.PubMedCrossRefGoogle Scholar
  63. Real, F. X., Oettgen, H. F., and Krown, S. E., 1986, Kaposi’s sarcoma and the acquired immunodeficiency syndrome: Treatment with high and low doses of recombinant leukocyte A interferon, J. Clin. Oncol. 4:544–551.PubMedGoogle Scholar
  64. Reddehause, M. J., Mutter, W., and Koszinowski, U. H., 1987, In vivo application of recombinant interleukin 2 in the immunotherapy of established cytomegalovirus infection, J. Exp. Med. 165:650–656.CrossRefGoogle Scholar
  65. Rook, A. H., Masur, H., Lane, H. C., Frederick, W., Kasahara, T., Macher, A. M., Djeu, J. Y., Manischewitz, J. F., Jackson, L., Fauci, A. S., and Quinnan, G. V., Jr., 1983, 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. 72:398–403.PubMedCrossRefGoogle Scholar
  66. Rosenthal, N. S., Hank, J. A., Kohler, P. C., Minkoff, D. Z., Moore, K. H., Bechhofer, R., Hong, R., Storer, B., and Sondel, P. M., 1988, The in vitro function of lymphocytes from 25 cancer patients receiving four to seven consecutive days of recombinant IL-2, J. Biol. Response Modif. 7:123–139.Google Scholar
  67. Schnittman, S. M., Vogel, S., Baseler, M., Lane, H. C., and Davey, R. T., Jr., 1994, A phase I study of interferon-α2b in combination with interleukin-2 in patients with human immunodeficiency virus infection, J. Infect. Dis. 169:981–989.PubMedCrossRefGoogle Scholar
  68. Schwartz, D. H., Skowron, G., and Merigan, T. C., 1991, Safety and effects of interleukin-2 plus zidovudine in asymptomatic individuals infected with human immunodeficiency virus, J. Acq. Immune Defic. Syndr. 4:11–23.Google Scholar
  69. Sheridan, J. F., Aurelian, L., Donnenberg, A. D., and Quinn, T. C., 1984, Cell-mediated immunity to cytomegalovirus (CMV) and herpes simplex virus (HSV) antigens in the acquired immune deficiency syndrome: Interleukin-1 and interleukin-2 modify in vitro responses, J. Clin. Immunol. 4:304.PubMedCrossRefGoogle Scholar
  70. Storek, J., Witherspoon, R. P., and Storb, R., 1995, T cell reconstitution after bone marrow transplantation into adult patients does not resemble T cell development in early life, Bone Marrow Transplant. 16:413–425.PubMedGoogle Scholar
  71. Teppler, H., Kaplan, G., Smith, K. A., Montana, A. L., Meyn, P., and Cohn, Z. A., 1993a, Prolonged immuno-stimulatory effect of low-dose polyethylene glycol interleukin 2 in patients with human immunodeficiency virus type 1 infection, J. Exp. Med. 177:483–492.PubMedCrossRefGoogle Scholar
  72. Teppler, H., Kaplan, G., Smith, K., Cameron, P., Montana, A., Meyn, P., and Cohn, Z., 1993b, Efficacy of low doses of the polyethylene glycol derivative of interleukin-2 in modulating the immune response of patients with human immunodeficiency virus type 1 infection, J. Infect. Dis. 167:291–298.PubMedCrossRefGoogle Scholar
  73. Toosi, Z., Kleinhenz, M. E., and Ellner, J. J., 1986, Defective interleukin 2 production and responsiveness in human pulmonary tuberculosis, J. Exp. Med. 163:1162–1172.CrossRefGoogle Scholar
  74. Volberding, P. A., and Mitsuyasu, R., 1985, Recombinant interferon-alpha in the treatment of acquired immune deficiency syndrome related Kaposi’s sarcoma, Semin. Oncol. 12:2–6.PubMedGoogle Scholar
  75. Volberding, P., Moody, D. J., Beardslee, D., Bradley, E. C., and Wofsy, C. B., 1987, Therapy of acquired immune deficiency syndrome with recombinant interleukin-2, AIDS Res. Hum. Retrovir. 3:115–124.PubMedCrossRefGoogle Scholar
  76. Waites, L., Fyfe, G., Senechek, D., and Vollmer, C., 1992, Polyethylene glycol modified interleukin-2 (PEG IL-2) therapy in HIV seropositive individuals [abstract No. PuB 7580], Program and Abstracts: VIII International Conference on AIDS, Amsterdam, Congrex Holland BV.Google Scholar
  77. Walker, R. E., Carter, C. S., Muul, L., Natarajan, V., Herpin, B. R., Leitman, S. F., Klein, H. G., Falloon, J., Davey, R. T., Kovacs, J. A., Polis, M. A., Masur, H., Blaese, R. M., and Lane, H. C., 1995, Survival and distribution of genetically modified cells in identical twins discordant for HIV-1 infection, AIDS Res. Hum. Retrovir. 11(Suppl. 1):S166.Google Scholar
  78. Wei, X., Ghosh, S. K., Taylor, M. E., Johnson, V A., Emini, E. A., Deutsch, P., Lifson, J. D., Bonhoeffer, S., Nowak, M. A., Hahn, B. H., Saag, M. S., and Shaw, G. M., 1995, Viral dynamics in human immunodeficiency virus type 1 infection, Nature 373:117–122.PubMedCrossRefGoogle Scholar
  79. Wood, R., Montoya, J. G., Kundu, S. K., Schwartz, D. H., and Merigan, T. C., 1993, Safety and efficacy of polyethylene glycol-modified interleukin-2 and zidovudine in human immunodeficiency virus type 1 infection: A phase I/II study, J. Infect. Dis. 167:519–525.PubMedCrossRefGoogle Scholar
  80. Zubiaga, A. M., Munoz, E., and Huber, B. T., 1992, IL-4 and IL-2 selectively rescue Th cell subsets from glucocorticoid-induced apoptosis, J. Immunol. 149:107–112.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Gwendolyn Anne Fyfe
    • 1
  • H. Clifford Lane
    • 2
  1. 1.Chiron CorporationEmeryvilleUSA
  2. 2.National Institutes of Health, National Institute for Allergy and Infectious DiseasesBethesdaUSA

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