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Intralymphatic interleukin-2 in combination with zidovudine for the therapy of patients with AIDS

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Summary

In a pilot study the safety and therapeutic effects of an immunostimulatory intralymphatic treatment with natural human interleukin-2 (IL-2) in combination with zidovudine were evaluated in nine patients with AIDS. Therapy with IL-2 consisted of one subcutaneous injection of 0.1 μg/kg IL-2, followed by four intralymphatic IL-2 infusions of 0.1 μg/kg each within a period of up to 15 days. Enlargement of lymph nodes was seen in six and a transient increase of CD4 cells in five out of nine persons in association with the IL-2 therapy. An increase of HIV p24-antigenemia was observed only in the two patients in whom zidovudine dosage had to be reduced because of side effects. Moderate clinical side effects occurred in eight of the nine patients. Four patients developed zidovudine associated anemia. Six participants showed a favourable course of disease with survival of 25 to 54 months (median 30 months) despite a previous diagnosis of manifest AIDS before IL-2 therapy. This pilot study demonstrates that a combination therapy with intralymphatic IL-2 and zidovudine can induce positive immunomodulatory effects, even in the presence of manifest AIDS. Further studies should explore the tolerability and effects of a prolonged therapy with IL-2 in combination with a more potent antiviral drug combination therapy.

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References

  1. Harrer, T., Messing, K., Bienzle, U., Meyer, E., Giedl, J., Kalden, J. R.: Manifestation von AIDS in HIV-infizierten homosexuellen Männern mit Lymphadenopathie-Syndrom (LAS). Klin. Wochenschr. 67 (1989) 936–939.

    Article  CAS  PubMed  Google Scholar 

  2. Rutherford, G. W., Lifson, A. R., Hessol, N. A., Darrow, W. W., O'Malley, P. M., Buchbinder, S. P., Barnhart, J. L., Bodecker, T. W., Cannon, L., Doll, L. S., Holmberg, S. D., Harrison, J. S., Rogers, M. F., Werdegar, D., Jaffe, H. W.: Course of HIV-1 infection in a cohort of homosexual and bisexual men: an 11 year follow-up study. Br. Med. J. 301 (1990) 1183–1188.

    Article  CAS  Google Scholar 

  3. Pantaleo, G., Graziosi, C., Demarest, J. F., Butini, L., Montroni, M., Fox, C. H., Orenstein, J. M., Kotler, D. P., Fauci, A. S.: HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362 (1993) 355–358.

    Article  CAS  PubMed  Google Scholar 

  4. Ebretson, J., Zupancic, M., Ribas, J. L., Burke, A., Racz, P., Tenner, R. K., Haase, A. T.: Massive covert infection of helper T lymphocytes and macrophages by HIV during incubation period of AIDS. Nature 362 (1993) 359–362.

    Article  Google Scholar 

  5. Caliendo, A. M., Hirsch, M. S.: Combination therapy for infection due to human immunodeficiency virus type 1. Clin. Infect. Dis. 18 (1994) 516–524.

    CAS  PubMed  Google Scholar 

  6. Moyle, G., Gazzard, B.: Current knowledge and future prospects for the use of HIV protease inhibitors. Drugs 5 (1996) 701–712.

    Google Scholar 

  7. Gramatzki, M., Nüsslein, H., Burmester, G. R., Rödl, W., Heyder, N., Grote, W., Monner, D. A., Mühlradt, P. F., Kalden, J. R.: Intralymphatic interleukin-2 treatment in patients with acquired immunodeficiency syndrome: preliminary experience in three cases. Immunobiology 172 (1986) 438–447.

    CAS  PubMed  Google Scholar 

  8. Alcocer-Varela, J., Alarcon-Segovia, D., Abud-Mendoza, C.: Immunoregulatory circuits in the acquired immune deficiency syndrome and related complex, production of and response to interleukins 1 and 2, NK function and its enhancement by interleukin-2 and kinetics of the autologous mixed lymphocyte reaction. Clin. Exp. Immunol. 60 (1985) 31–38.

    CAS  PubMed  Google Scholar 

  9. Murray, H. W., Welte, K., Jacobs, J. L., Rubin, B. Y., Mertelsmann, R., Roberts, R. B.: Production of andin vitro response to interleukin-2 in the acquired immunodeficiency syndrome. J. Clin. Invest. 76 (1985) 1959–1964.

    Article  CAS  PubMed  Google Scholar 

  10. Ciobanu N., Welte, K., Kruger, G., Salvatore, V., Gold, J., Feldman, S. P., Wang, C. Y., Koziner, B., Moore, M. A. S., Bijan, S., Mertelsmann, R.: Defective T-cell response to PHA and mitogenic monoclonal antibodies in male homosexuals with acquired immunodeficiency syndrome and itsin vitro correction by interleukin-2. J. Clin. Immunol. 3 (1993) 332–340.

    Article  Google Scholar 

  11. Rotzschke, O., Falk, K., Deres, K.: Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 348 (1990) 252–254.

    Article  CAS  PubMed  Google Scholar 

  12. Lifson, J. D., Benike, C., Mark, D. F., Koths, K., Engleman, E. G.: Human recombinant interleukin-2 partly reconstitutes deficientin vitro immune responses of lymphocytes from patients with AIDS. Lancet i (1984) 698–702.

    Article  Google Scholar 

  13. 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., Quinnan, G. V.: 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 (1983) 398–403.

    Article  CAS  PubMed  Google Scholar 

  14. Lotze, M. T., Matory, Y. L., Ettinghausen, S. E., Rayner, A. A., Sharrow, S. O., Seipp, C. A. Y., Custer, M. C., Rosenberg, S. A.:In vitro administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cellsin vivo with recombinant IL 2. J. Immunol. 135 (1985) 2865–2875.

    CAS  PubMed  Google Scholar 

  15. Siegel, J. P., Puri, R. K.: Interleukin-2 toxicity. J. Clin. Oncol. 9 (1991) 694–704.

    CAS  PubMed  Google Scholar 

  16. Gramatzki, M., Burmester, G. R., Heyder, N., Nüßlein, H. G., Rödl, W., Grote, W., Monner, D. A., Mühlradt, P. F., Kalden, J. R.: Intralymphatic interleukin-2 treatment of a hemophiliac AIDS patient with defective interleukin-2 production. Klin. Wochenschr. 65 (1987) 380–386.

    Article  CAS  PubMed  Google Scholar 

  17. Centers for Disease Control: 1992 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 41 (1993) 1–19.

    Google Scholar 

  18. Hubbard, R. D., Collins, F. M.: Immunomodulation of mouse macrophage killing ofMycobacterium avium in vitro. Infect. Immun. 59 (1998) 570–574.

    Google Scholar 

  19. Bermudez, L. E., Stevens, P., Kolonoski, P., Wu, M., Young, L. S.: Treatment of experimental disseminatedMycobacterium avium complex infection in mice with recombinant IL-2 and tumor necrosis factor. J. Immunol. 143 (1998) 2996–3000.

    Google Scholar 

  20. Blanchard, D. K.: Cytokine activation of killer cells in mycobacterial immunity. Adv. Exp. Med. Biol. 319 (1998) 105–112.

    Google Scholar 

  21. Kovacs, J. A., Baseler, M., Dewar, R. J., Vogel, S., Dayvey, R. T., Falloon, J., Polis, M. A., Walker, R. E., Stevens, R., Salzman, N. P., Metcalf, J. A., Masur, H., Lane, C.: Increases in CD4 T lymphocytes with intermittent courses of interleukin-2 in patients with human immunodeficiency virus infection. N. Engl. J. Med. 332 (1995) 567–575.

    Article  CAS  PubMed  Google Scholar 

  22. Schnittman, S. M., Vogel, S., Baseler, M., Lane, H. C., Davey, R. T.: A phase I study of interferon-alpha 2b in combination with interleukin-2 in patients with human immunodeficiency virus infection. J. Infect. Dis. 169 (1994) 981–989.

    CAS  PubMed  Google Scholar 

  23. Clark, A. G. B., Holdniy, M., Schwartz, D. H., Katzenstein, D. A., Merigan, T. C.: Decrease in HIV provirus in peripheral blood mononuclear cells during zidovudine and human rIL-2 administration. J. Acquir. Immune Defic. Syndr. 5 (1992) 52–59.

    CAS  PubMed  Google Scholar 

  24. Wood, R., Montoya, J. G., Kundu, S. K., Schwartz, D. H., Merigan, T. C.: 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 (1993) 519–525.

    CAS  PubMed  Google Scholar 

  25. Kovacs, J. A., Vogel, S., Jeffrey, M. A., Folloon, J., Davey, R. T., Walker, R. E., Polis, M. A., Spooner, K., Metcalf, J. A., Baseler, M., Fyfe, G., Lane, H. C.: Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus. N. Engl. J. Med. 335 (1996) 1350–1356.

    Article  Google Scholar 

  26. Walker, C., Moody, D., Stites, D., Levy, J.: CD8+ lymphocytes can control HIV infectionin vitro by suppressing virus replication. Science 234 (1986) 1563–1566.

    Article  CAS  PubMed  Google Scholar 

  27. Walker, B. D., Flexner, C., Paradis, T. J., Fuller, T. C., Hirsch, M. S., Schooley, R. T., Moss, B.: HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. Science 240 (1988) 64–66.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medizinische Klinik III, Universität Erlangen-Nürnberg, Krankenhausstr. 12, D-91054, Erlangen, Germany

    T. Harrer, J. Schwab, M. Schmitt, J. R. Kalden & M. Gramatzki

  2. Medizinische Klinik I, Universität Erlangen-Nürnberg, Erlangen, Germany

    J. H. Ficker

  3. Röntgenabt. der Medizinischen Klinik der Universität Erlangen-Nürnberg, Erlangen, Germany

    W. Rödl

  4. Zentrallabor der Universität Erlangen-Nürnberg, Erlangen, Germany

    H. Parsch

  5. Biotest Pharma GmbH, D-63303, Dreieich, Germany

    W. G. Struff

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  1. T. Harrer
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  2. J. Schwab
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  3. W. G. Struff
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  4. M. Schmitt
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  5. J. H. Ficker
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  6. W. Rödl
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  7. H. Parsch
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  8. J. R. Kalden
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  9. M. Gramatzki
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Harrer, T., Schwab, J., Struff, W.G. et al. Intralymphatic interleukin-2 in combination with zidovudine for the therapy of patients with AIDS. Infection 26, 368–374 (1998). https://doi.org/10.1007/BF02770838

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  • DOI: https://doi.org/10.1007/BF02770838

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