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Title

Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome

Authors
Cerny, A.
Merino, Ramon
Fossati-Jimack, Liliane
de Kossodo, S.
Heusser, C.
Morse, H. C.
Published in Journal of Infectious Diseases. 1992, vol. 166, no. 2, p. 285-290
Abstract 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.
Keywords AnimalsCyclosporine/pharmacology/ therapeutic useDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHypergammaglobulinemia/drug therapyLymph Nodes/pathologyLymphocyte Activation/drug effectsMiceMice, Inbred C57BLMurine Acquired Immunodeficiency Syndrome/ drug therapy/immunologyRetroviridae Proteins, Oncogenic/bloodViral Envelope Proteins/bloodZidovudine/pharmacology/ therapeutic use
Stable URL http://archive-ouverte.unige.ch/unige:10877
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PMID: 1634800
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