Antiviral efficacy and toxicity of ribavirin in murine acquired immunodeficiency syndrome model.
The antiretroviral efficacy and hematotoxicity of ribavirin, a guanosine analogue, have been evaluated in mice infected with the LP-BM5 virus pool [murine acquired immunodeficiency syndrome (MAIDS) model]. Doses ranging from 6.25 to 200 mg/kg/day were injected intraperitoneally twice a day for 6 weeks to infected mice. Drug treatment induced a significant protection against splenomegaly and lymphadenopathy at doses > or = 25 mg/kg. Moreover, doses starting at 50 mg/kg protected against hypergammaglobulinemia, minimized the loss of spleen CD8+ T cells, and reconstituted the capacity of splenocytes to proliferate in response to concanavalin A. The spleen and cervical lymph node architectures were protected, and a reduction in the emergence of germinal centers was observed at 50 mg/kg ribavirin. Hematotoxicity appeared at doses > or = 50 mg/kg ribavirin, and severe anemia was predominant only at doses of 100 and 200 mg/kg. This study shows that ribavirin protects mice against the effects resulting from retrovirus infection at doses of > or = 50 mg/kg in a MAIDS model and induces severe hematotoxicity at doses > or = 100 mg/kg.
Harvie
P
P
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval, Québec, Canada.
Omar
R F
RF
Dusserre
N
N
Désormeaux
A
A
Gourde
P
P
Tremblay
M
M
Beauchamp
D
D
Bergeron
M G
MG
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001772:Blood Cell Count; D016516:CD4-CD8 Ratio; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D007075:Immunoglobulin M / Q000097:blood; D009052:Leukemia Virus, Murine; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D009929:Organ Size; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D013154:Spleen / Q000166:cytology / Q000473:pathology
D000998:Antiviral Agents; D007075:Immunoglobulin M; D003208:Concanavalin A; D012254:Ribavirin