Recombinant immune interferon inhibits leukemic cell growth by a monocyte-macrophage-mediated mechanism.

We have investigated direct and monocyte-macrophage (Mono/M phi)-mediated indirect effects of recombinant immune interferon (IFN-gamma) on the growth of established leukemic cell lines (K562, KG1, ML1, HL60, U937, and THP1). The direct antiproliferative effects of IFN-gamma on these leukemic cells were mild or negligible, when estimated by 3H-thymidine incorporation. Indirect effects were assessed by the growth pattern of leukemic cells cocultured with Mono/M phi that were pretreated with INF-gamma. While the leukemic cell growth was slightly suppressed by untreated Mono/M phi, this suppression was significantly augmented by the treatment of Mono/M phi with IFN-gamma (10-10,000 U/ml). In addition, the indirect effects of IFN-gamma on leukemic cell growth were examined at different stages of maturation of Mono/M phi. The augmentation of cytotoxicity was detected only when mature Mono/M phi were treated with INF-gamma. This suggests that IFN-gamma acts on tissue macrophages and augments their cytotoxicity against leukemic cells.