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.
D002455:Cell Division; D002460:Cell Line; D004274:DNA, Recombinant; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D007938:Leukemia / Q000473:pathology / Q000628:therapy*; D007951:Leukemia, Myeloid / Q000473:pathology / Q000628:therapy; D008223:Lymphoma / Q000473:pathology / Q000628:therapy; D008264:Macrophages / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D013997:Time Factors
D004274:DNA, Recombinant; D007371:Interferon-gamma