Comparative analysis of the immunosuppressive properties of two antiviral, iodinated thymidine analogs, 5-iodo-2'-deoxyuridine and 5-iodo-5'-amino-2',5'-dideoxyuridine.
5-Iodo-5'-amino-2',5'-dideoxyuridine (AldUrd), given as five single i.p. injections on Days 0 to 4 after antigenic challenge with sheep erythrocytes, had no demonstrable effect on serum hemagglutinin titers in doses as high as 2000 mg/kg/day. This was the maximum feasible single dose, but no 10% lethal dose was determinable. Similarly, 5-iodo-2'-deoxyuridine (IdUrd), 50 mg/kg/day (10% lethal dose), on Days 0 to 4 did not significantly affect this humoral response. However, with a more sensitive assay, immunocytoadherence, reductions in the number of hemagglutinin-forming cells in the spleen were found at several levels of AldUrd and IdUrd, but the same level of inhibition was attained by a course of AldUrd, 2000 mg/kg, or IdUrd, 50 mg/kg. Spleen cell-mediated immunity against lethally irradiated L1210 was measured by 4-hr 51Cr release and 48-hr growth inhibition assays. Both drugs showed dose-related immunosuppression. With AldUrd, 2000 mg/kg/day, and IdUrd, 100 mg/kg/day, on Days 0 to 4, cytotoxicity was inhibited by 35 to 68% and 73 to 90%, respectively. In comparison, a similar course of 1-beta-D arabinofuranosylcytosine, 40 mg/kg/day, completely abrogated both humoral and cell-mediated immunity. When AldUrd and IdUrd were administered on Days -5 to -1, little effect on either type of immunity was found, while pretreatment with the alkylating agent, cyclophosphamide, abolished all T-cell-mediated killing as measured on Day 7. Thus, AldUrd appears to be a very mild and IdUrd a moderate to strong cell cycle-dependent immunosuppressive.
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006388:Hemagglutinins / Q000032:analysis; D007065:Idoxuridine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000276:immunology; D008297:Male; D051379:Mice; D012397:Rosette Formation; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D006388:Hemagglutinins; D007166:Immunosuppressive Agents; C021283:5'-amino-5-iodo-2',5'-dideoxyuridine; D007065:Idoxuridine