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 10⁵ 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 10⁴ marrow cells, 20% of rmGM-CSF treated mice survived as compared with none in the controls. In vitro preincubation of 10⁵ and 5x10⁵ 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.