Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome
|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||Animals — Cyclosporine/pharmacology/ therapeutic use — Dose-Response Relationship, Drug — Drug Therapy, Combination — Female — Hypergammaglobulinemia/drug therapy — Lymph Nodes/pathology — Lymphocyte Activation/drug effects — Mice — Mice, Inbred C57BL — Murine Acquired Immunodeficiency Syndrome/ drug therapy/immunology — Retroviridae Proteins, Oncogenic/blood — Viral Envelope Proteins/blood — Zidovudine/pharmacology/ therapeutic use|
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