Radioprotective Effects of Various Cytokines in Peripheral Blood Mononuclear Cells and C3H Mice

The purpose of this study was to investigate the radioprotective effect of HGFs (GM-CSF, IL-3 and SCF) in irradiated human peripheral blood mononuclear cells (PBMCs) in vitro, and the survival effect of lethally irradiated C3H mice in vivo. The irradiation of human PBMCs using a (137)Cs irradiator showed a dose-dependent inhibition of cell growth up to a dose of 5 Gy. This cell growth inhibition induced apoptosis, which was associated with the down-regulation of Bcl-2, up-regulation of Bax, depolarization of mitochondrial transmembrane potential (Delta psi m), and caspase-3 and -9 activation. Following gamma-irradiation at 2 Gy, IL-3 (10 ng/ml) alone or combined with SCF (50 ng/ml) reduced the apoptotic portion of human PBMCs by 15 and 20% of the cell population, respectively, showing no activation of caspase-3 compared to the control group. To examine the in vivo effect of gamma-irradiation and cytokines, we investigated the survival rate and recovery of peripheral blood cells in C3H mice. C3H mice subjected to total body irradiation (TBI) at a dose of 7 Gy (lethal dose 83% at 30 days) showed time-dependent decreases in RBC, WBC and platelet counts, with the nadir occurring at 12 to 15 days. However, treatment with recombinant murine (rm) SCF (2 microg/day s.c.), rmIL-3 (2 microg/day s.c.), or rmG-CSF (2.5 microg/day s.c.) 24 h before and after irradiation did not promote hematologic recovery or survival in the lethally irradiated C3H mice. These findings indicate that the combined treatment of IL-3 and SCF prevents the apoptosis induced in PBMCs by gamma-irradiation in vitro, but it does not afford any in vivo radioprotective effect in lethally irradiated C3H mice.