Immunosuppressive activity of 4′-iodo-4′-deoxy-doxorubicin on humoral and cell mediated immune responses in mice: Comparison with doxorubicin

Abstract

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.