ABSTRACT
The aim of this study was to investigate the radioprotective effect of recombinant murine interleukin 12 (rmIL-12) on mice irradiated by γ-ray. Fifty- six BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group,rmIL-12 treated group and recombinant murine thrombopoietin (rmTPO) treated group.The 5 and 20 µg/kg of rmIL-12 were administrated intraperitoneally at 24 h before irradiation respectively (low and high dose rmIL-12 treated group), 15 µg/kg of rmTPO was administrated subcutaneously at 30 min and 24 h following irradiation in rmTPO treated group. The general conditions of mice were observed twice a day, the changes in body weight and peripheral blood cell counts were examined once every three days, bone marrow cells were collected to perform colony cultivation at day 14 and 28 after irradiation. The results showed that the general conditions of mice in rmIL-12 treated group were better than those in irradiation control group. Compared with the irradiation control group,5 and 20 µg/kg rmIL-12 treatment significantly promoted platelet recovery, resulting in less profound nadirs (15.9% vs 8.1%,18.2% vs 8.1%,P < 0.01) and rapid recovery to normal levels (11 days vs 14 days). WBC count recovery rate in rmIL-12 treated group was faster than that in the irradiation control group. The WBC and platelet count recovery rate in 5 µg/kg rmIL-12 treated group were as fast as that in the rmTPO treated group, both of which were slower than that in 20 µg/kg rmIL-12 treated group (P > 0.05). Semi-solid bone marrow cell culture also demonstrated that rmIL-12 could stimulate bone marrow cells to form more CFU-Mix than those in the irradiation control group in vitro at day 14 and 28 after irradiation(P < 0.01).There was no significant difference between rmIL-12 and rmTPO treated groups (P > 0.05), CFU-GM counts in 5 µg/kg rmIL-12 treated group and rmTPO treated group at day 28 after irradiation were higher than those in irradiation control group(P < 0.05), but less than those in 20 µg/kg rmIL-12 treated group (P < 0.05). It is concluded that rmIL-12 has a significant radioprotective effect on mice irradiated by γ-ray.
Subject(s)
Animals , Male , Mice , Blood Platelets , Gamma Rays , Interleukin-12 , Therapeutic Uses , Mice, Inbred BALB C , Platelet Count , Radiation Injuries, Experimental , Blood , Radiation-Protective Agents , Therapeutic Uses , Recombinant Proteins , Therapeutic Uses , Thrombopoietin , Therapeutic Uses , Whole-Body IrradiationABSTRACT
The aim of this study is to observe the therapeutic effect of recombinant murine interleukin 12 (rmIL-12) combining with granulocyte colony stimulating factor (G-CSF) on mice irradiated by γ-rays. 56 BALB/c mice were totally irradiated by 6.0 Gy of (60)Co γ-ray and randomly divided into irradiation control group, rmIL-12 treatment group, G-CSF treatment group and combination therapy (rmIL-12 plus G-CSF) group. rmIL-12 20 µg/kg was administrated intraperitoneally at 1 h following irradiation, and was administrated every 3 days after irradiation for 4 times in rmIL-12 treatment group. G-CSF 100 µg/kg was administrated subcutaneously the 2 h following irradiation for 14 d in G-CSF treatment group. The dose and method of rmIL-12 and G-CSF in combination therapy group were same as in rmIL-12 group and G-CSF group. The general status of mice were observed twice a day, the changes in body weight, peripheral blood cell (WBC and Plt) counts were examined once every three days, bone marrow cells were collected to perform colony cultivation on day 14 and 28 after irradiation. The results showed that WBC count recovery time in combination therapy group was significantly earlier than that of the control group (7 d vs 11 d), WBC count recovery velocity in the combination therapy group was no significant different from that of the G-CSF treatment group. Combined therapy significantly promoted Plt count recovery, resulting in less profound nadirs (16.5% vs 8.1%, P < 0.01) and rapid recovery to normal levels (11 d vs 14 d), Plt count recovery velocity in the combination therapy group was no significant different from that of the rmIL-12 treatment group. Culture of bone marrow cells in semi-solid medium also demonstrated that combination of rmIL-12 and G-CSF could stimulate bone marrow cells to form more CFU-GM and CFU-Mix than those of the irradiation control group in vitro on day 14 and 28 after irradiation (P < 0.05). It is concluded that the combination of rmIL-12 and G-CSF can significantly accelerate the recovery of hematopoietic function in mice with acute radiation sickness.