Immunosuppressive activity of 4'-iodo-4'-deoxy-doxorubicin on humoral and cell mediated immune responses in mice: comparison with doxorubicin.
4'-Iodo-4'-deoxy-doxorubicin (I-DX) is a new halogenated doxorubicin (DX) derivative, selected for clinical testing in view of a number of pharmacotoxicological advantages vis-à-vis the parental compound. It was thus of interest to compare the immunological effects of I-DX to those of DX. The compounds were injected i.v. into mice at equal doses in terms of acute toxicity, over a variety of treatment schedules. When tested in single doses for anti SRBC primary and secondary antibody response, I-DX, unlike DX, was not immunodepressive; on the contrary it often caused a moderate amplification of the response. Following a multiple treatment schedule, I-DX was as depressive as DX only when administered after the antigen, any other treatment regimen, before or concomitant with the antigen, being uneffective. I-DX was completely uneffective and DX only slightly active in delaying skin allograft rejection and in reducing DTH reactivity to SRBC. I-DX was more inhibitory than DX for lymphoid cells in vitro, and both drugs reduced spleen cellularity without modifying the relative percentage of B and T cells after administration in vivo. However, the splenic reactivity to LPS ex vivo, unlike that to ConA, was restored earlier in I-DX than in DX-treated mice.
Isetta
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AM
Farmitalia Carlo Erba, Research Center, Nerviano (Mi), Italy.
Fornasiero
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MC
Ferrari
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D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006968:Hypersensitivity, Delayed; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D007166:Immunosuppressive Agents; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin