Continuous intravenous administration of rmGM-CSF enhances immune as well as hematopoietic reconstitution following syngeneic bone marrow transplantation in mice.
Lethally irradiated Balb/c mice injected with syngeneic bone marrow cells received recombinant murine granulocyte/macrophage colony-stimulating factor (rmGM-CSF) by continuous intravenous infusion for 4 days. When transplanted with 10(5) marrow cells, treated mice showed higher survival (62% compared with 30% in the control group, p < 0.001) and significantly enhanced hematopoietic recovery manifested by 11-fold increase in the peripheral white blood cell (WBC) count. Day 7 marrow from rmGM-CSF-treated mice resulted in 70% survival in lethally irradiated secondary recipients, while marrow harvested under identical experimental conditions from saline-treated mice had no reconstituting capacity at all. When mice were injected with 10(4) marrow cells, 20% of rmGM-CSF treated mice survived as compared with none in the controls. In vitro preincubation of 10(5) and 5 x 10(5) fresh bone marrow cells with rmGM-CSF prior to transplant significantly improved survival of lethally irradiated mice in comparison with control (12% and 37.5% respectively, p < 0.001). Proliferative responses of lymphocytes obtained from rmGM-CSF-treated mice to mitogens and allogeneic C57BL6 splenocytes as well as non-MHC restricted cytotoxicity against tumor cells were significantly higher in rmGM-CSF-treated mice as compared with controls (p < 0.01). These data suggest that a short course of continuous intravenous infusion of rmGM-CSF following BMT or in vitro culturing of bone marrow cells with rmGM-CSF improves marrow reconstituting capacity. The mechanism may be by enhancing proliferation and function of committed and perhaps even the more primitive progenitor cell.
Naparstek
E
E
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Ohana
M
M
Greenberger
J S
JS
Slavin
S
S
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D003208:Concanavalin A / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006410:Hematopoiesis; D007109:Immunity; D007262:Infusions, Intravenous; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010835:Phytohemagglutinins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014916:Whole-Body Irradiation
D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D011994:Recombinant Proteins; D003208:Concanavalin A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor