AUGMENTATION OF HEMATOPOIESIS BY FIBROBLAST-MEDIATED INTERLEUKIN-6 GENE-THERAPY IN MICE WITH CHEMOTHERAPY

Murine fibroblast NIH3T3 cells engineered to secrete interleukin-6 (NI H3T3-IL-6) were implanted intraperitoneally into mice and observed for their hematopoietic effects with or without 5-fluorouracil (5-FU) adm inistration. In normal mice, the platelet and neutrophil counts in per ipheral blood increased significantly after implantation of NIH3T3-IL- 6 cells, but the total white blood cell numbers showed no obvious elev ation. The granulocyte-macrophage colony-forming unit (CFU-GM) and meg akaryocyte colony-forming unit (CFU-MK) numbers formed by stem cells i n bone marrow and spleen were also found to be significantly increased after implantation of NIH3T3-IL-6 cells when compared with those in m ice after implantation of NIH3T3 cells transduced with neomycin gene ( NIH3T3-Neo). To observe the protective effects of NIH3T3-IL-6 cells on hematopoietic depression in chemotherapy-treated mice, the mice were preinjected with 5-FU at a dosage of 150 mg/kg before implantation of NIH3T3-IL-6 cells. The platelet and neutrophil counts showed accelerat ed recovery after implantation of NIH3T3-IL-6 cells. The numbers of CF U-GM and CFU-MK in bone marrow and spleen were also found to be marked ly increased in hematopoietic-depressed mice when compared with those in mice implanted with NIH3T3-Neo cells. These data suggest that fibro blast-mediated IL-6 gene therapy, which can augment hematopoiesis in m ice with or without chemotherapy, will be of great help in the recover y from hematopoietic depression after chemotherapy.