Correlation between Adriamycin-induced Augmentation of Interleukin 2 Production and of Cell-mediated Cytotoxicity in Mice1

Based on the observation that spleen cells from Adriamycintreated mice could develop augmented levels of cytotoxic Tlymphocyte activity in response to heat-treated and/or X-irradiated alloantigens, it was postulated that modulations in soluble mediators could be involved in this phenomenon. In fact, in this study Adriamycin-induced increases in the levels of prostaglandin E2 and interleukin 2 activity have been observed with isolated cells. The "interleukin 2-like" activity was indistinguishable from that of partially purified interleukin 2 in terms of ability to restore responsiveness to experimentally inhibited primary alloantigen response cultures and to maintain long-term cultures of activated T-cells. Furthermore this latter activity was completely ablated by antiinterleukin 2 monoclonal antibody. While the modification in prostaglandin E, production did not appear to play a role in determining augmentation of cytotoxic T-cell activity, the modi fication in interleukin 2 production was consistent with the pos sibility that this is a primary mechanism of Adriamycin-induced augmented cell-mediated cytotoxicity.