Comparison of adriamycin induced immunomodulation with that of the noncardiotoxic anthracycline 5-iminodaunorubicin.
Adriamycin (ADM) has been shown to modulate a variety of host immune responses. Although the mechanism(s) for this activity is not known, it has been suggested that free radical compounds generated during ADM metabolism act at the membrane level to alter immune cell function. The generation of free radical metabolites is also believed to be responsible for the cardiotoxic potential of ADM. 5-Iminodaunorubicin (IDM) is a non-cardiotoxic anthracycline analog which undergoes minimal free radical metabolism. In the present study the immunomodulatory capacity of IDM was compared to that of ADM. It was found that IDM and ADM had similar augmenting effects on cytolytic T-cell activity and that this correlated with: (1) Fc-dependent phagocytosis by spleen cells; and (2) the elimination or inhibition of an adherent regulatory cell in the spleen. The natural killer response was either unaffected (fresh NK) or slightly inhibited (cultured NK) by both drugs except moderate dose IDM which resulted in marked augmentation of cultured NK.
Maccubbin
D L
DL
Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Whitman
J A
JA
Taniguchi
N
N
Mace
K F
KF
Ehrke
M J
MJ
Mihich
E
E
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology*; D005260:Female; D007694:Killer Cells, Natural / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis / Q000187:drug effects; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects
D000276:Adjuvants, Immunologic; D004317:Doxorubicin; C018979:5-iminodaunorubicin; D003630:Daunorubicin