DOSE-RESPONSE AND TIMING EFFECTS IN THE THERAPY OF THE LP-BM5 MURINE RETROVIRUS-INDUCED LYMPHOPROLIFERATIVE IMMUNODEFICIENCY DISEASE WITH DIETHYLDITHIOCARBAMATE

Diethyldithiocarbamate (DTC) was used to treat the murine, retrovirus-induced, immunodeficiency disease (MAIDS). Once-weekly treatment was not effective and 800 mg/kg was toxic. When 200, 400 and 600 mg/kg were given i.p., 5 days per week, starting either on the day of virus inoculation or 14 days later, a dose - response and time - response relationship was noted. Higher doses and a 2-week delayed onset of treatment were generally more effective in reducing the development of lymphadenopathy, hypergammaglobulinemia and in prolonging survival than treatment started on the day of virus inoculation. When treatment was delayed until 10 weeks after virus inoculation existing lymphadenopathy was abrogated (treated node area 0 mm2 compared to control 175 mm2, P<0.0001) and survival was improved (treated 100% compared to control 12.5%, P<0.0001). However, when therapy was stopped animals died at the same rate as the untreated controls. These data indicate that DTC is active in MAIDS in a dose-responsive and time-dependent manner.