In vitro effects of an antitumor antibiotic, ascofuranone, on the murine immune system.

Effects of an antitumor antibiotic, ascofuranone (AF) on the murine immune system were studied. Unlike lectins, AF did not induce any proliferative response of splenocytes. Furthermore, AF significantly inhibited proliferative response of splenocytes in response to lectins, such as concanavalin A, lipopolysaccharide, or phytohemagglutinin above 5 micrograms/ml. In concanavalin A-induced T-lymphocyte response, AF selectively inhibited the formation of interleukin 2 (IL-2) receptors, which was observed above 0.4 micrograms/ml. On the other hand, the inhibitory effect on the proliferative response to IL-2 of T-lymphocytes, which had already obtained IL-2 receptors, was observed above 10 micrograms/ml. IL-2 production of splenocytes in response to concanavalin A was also suppressed by AF above 2 micrograms/ml and only 3% of IL-2 was produced in the presence of AF, 10 micrograms/ml. However, AF-activated macrophages and their glycolysis was significantly stimulated. Activation of macrophages by AF was also confirmed by stimulation of interleukin 1 production and tumoricidal activity. However, natural killer activity of splenocytes was suppressed at the concentration where significant activation of tumoricidal activity of macrophages was observed. Therefore, AF had a dual effect on the immune system. Macrophages were activated to produce interleukin 1 and to kill tumor cells. On the other hand, functions of lymphocytes were suppressed.