R. Zagozdzon et al., The potentiated antileukemic effects of doxorubicin and interleukin-12 combination are not dependent on nitric oxide production, CANCER LETT, 147(1-2), 1999, pp. 67-75
In our recent study we described a significant antileukemic efficacy of a c
ombination therapy with interleukin-12 (IL-12) and doxorubicin (DOX) in the
L1210 leukemia model. This therapeutic effect was abrogated by elimination
of activated macrophages. Activated macrophages produce a variety of facto
rs that can contribute to the elimination of tumor cells in vivo, including
proteases, TNF, reactive oxygen intermediates, and nitric oxide (NO). Base
d on the results of previous reports, the contribution of NO in potentiated
antileukemic effects of IL-12 + DOX combination seemed to be highly possib
le. Both DOX and IL-12 given alone increased the production of NO by perito
neal macrophages, however, macrophages derived from the mice treated with t
he combination of those agents produced significantly less NO than macropha
ges from IL-12-alone-treated mice. Production of NO by spleen macrophages a
fter IL-12 + DOX treatment was higher than it was in controls, IL-12-alone-
or DOX-alone-treated groups. In serum, concentrations of NOx- in IL-12- or
IL-12 + DOX-treated mice were significantly higher in comparison with contr
ols, however not significantly different from each other. Addition of L-NAM
E treatment to the IL-12 + DOX therapy in leukemia-bearing mice did not sig
nificantly change the antileukemic efficacy of this therapy. Thus, our resu
lts indicate that the augmented antileukemic effects of IL-12 + DOX combina
tion therapy in L1210 model are NO-independent. Therefore, further studies
on the possible mechanisms of potentiated antileukemic activity of combinat
ion of IL-12 and DOX would be worth pursuing. (C) 1999 Elsevier Science Ire
land Ltd. All rights reserved.