Effect of cyclosporin A and zidovudine on immune abnormalities observed in the murine acquired immunodeficiency syndrome.
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.
Cerny
A
A
Department of Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Merino
R
R
Fossati
L
L
de Kossodo
S
S
Heusser
C
C
Waldvogel
F A
FA
Morse
H C
HC
Izui
S
S
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006942:Hypergammaglobulinemia / Q000188:drug therapy; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000097:blood; D014759:Viral Envelope Proteins / Q000097:blood; D015215:Zidovudine / Q000494:pharmacology / Q000627:therapeutic use*
D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins; D015215:Zidovudine; D016572:Cyclosporine