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Effect of Cyclosporin A and Zidovudine on Immune Abnormalities Observed in the Murine Acquired Immunodeficiency Syndrome

Cerny, Andreas ; Merino, Ramón ; Fossati, Liliane ; de Kossodo, Sylvie ; Heusser, Christoph ; Waldvogel, Francis A. ; Morse, Herbert C. ; Izui, Shozo

In: Journal of Infectious Diseases, 1992, vol. 166, no. 2, p. 285-290

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    Title
    • Effect of Cyclosporin A and Zidovudine on Immune Abnormalities Observed in the Murine Acquired Immunodeficiency Syndrome
    Author
    • Cerny, Andreas. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • Merino, Ramón. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • Fossati, Liliane. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • de Kossodo, Sylvie. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • Heusser, Christoph. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • Waldvogel, Francis A.. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • Morse, Herbert C.. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    • Izui, Shozo. Departments of Medicine and Pathology, Hôipital Cantonal Universitaire, Geneva, Switzerland;, Basel, Switzerland, Bethesda, Maryland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Journal of Infectious Diseases, 1992, vol. 166, no. 2, p. 285-290. The University of Chicago Press
    Other Version
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:301259
    Summary
    Two therapeutic modalities, zidovudine (targeting retroviral replication) and cyclosporin A (targeting immunopathologic consequences of retroviral expression) were evaluated in a murine model of AIDS. In previous studies, cyclosporin A treatment (40 or 60 mg/kg/day) before and after infection with LP-BM5 murine leukemia viruses protected against the development of immunodeficiency disease. The present study extends these findings. First, a low dose of cyclosporin A (20 mg/kg/day) was ineffective, and treatment initiated 5 days after infection did not protect against virus-induced lymphoproliferation and hypergammaglobulinemia. Second, zidovudine added to drinking water (0.1 mg initiated 5 days after infection and continued for 8 weeks) was more effective than 0.2 mg/ml, given day 5-12 after infection. This treatment reduced lymph node size, disease severity as determined histologically, retrovirus-induced gp70 expression, and IgE (but not IgM and IgG) levels. Third, combined treatment had an additive, protective effect on lymphocyte proliferative capacity. This successful dual therapeutic strategy in a mouse model has potential applicability for similar approaches in treating human immunodeficiency virus infection