Progressive murine cytomegalovirus disease after termination of ganciclovir therapy in mice immunosuppressed by cyclophosphamide treatment.
Treatment of mice with cyclophosphamide causes immunosuppression and an enhancement of murine cytomegalovirus infection. In chemotherapy experiments, animals received cyclophosphamide (100 mg/kg by intraperitoneal [ip] injection) every 3-4 days starting 1 day before viral challenge. Once-daily ip treatments with ganciclovir (12.5, 25, and 50 mg/kg) for 5 or 10 days starting 24 h after viral challenge delayed but did not prevent death. In each case the animals died 8-12 days after the last dose of drug was given. Murine cytomegalovirus titers in tissues were suppressed during ganciclovir treatments but rose with discontinuation of therapy. Concanavalin A (T cell blastogenic) responses and, to a lesser extent, lipopolysaccharide (B cell blastogenic) responses were increased in ganciclovir-treated mice compared with the placebo group. Because of the progressive nature of the infection after termination of drug treatment, this model mimics the situation encountered in AIDS patients. The cyclophosphamide model will be useful to study drug treatment regimens.
Smee
D F
DF
Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan 84322.
Burger
R A
RA
Coombs
J
J
Huffman
J H
JH
Sidwell
R W
RW
D000818:Animals; D003520:Cyclophosphamide / Q000633:toxicity*; D003587:Cytomegalovirus / Q000187:drug effects / Q000254:growth & development; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D012469:Salivary Glands / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D015430:Weight Gain / Q000187:drug effects
D003520:Cyclophosphamide; D015774:Ganciclovir