ABSTRACT
Hemorrhage is one of major clinical features of the patients exposed to large dose of ionizing radiation and a sudden decrease of peripheral platelet counts in hemorrhage complication may bring the patients into life-threatening situation. Cytokines had been used to improve thrombocytopoiesis in various radiation induced thrombocytopenia. Current measures for this purpose involve repeated injection of recombinant cytokines, which bring much inconvenient and agony to the patients, or gene therapy with viral vectors that could not obviate the risk of infection. This work tried to determine the possibility of gene therapy with plasmid vectors for radiation-induced hematopoietic injury. After a single intramuscular injection of plasmid hIL-6 cDNA on 6.5 Gy irradiated mice, the IL-6 level began to increase from the day 4, reached the peak value about the day 11 and maintained at a higher level on the day 28, but the hIL-6 level showed less changes in unirradiated mice. Further experiments demonstrated the IL-6 level in 7.5 Gy irradiated mice was about three times higher than that of 5.0 Gy irradiated mice and the expression of hIL-6 in vivo showed significant effect on hematopoietic recovery. Not only the platelet nadir in peripheral blood, but also the number of colony-forming cells in bone marrow rose. It is concluded that radiation could significantly enhance the gene transfer efficiency of plasmid DNA and gene therapy with plasmid vectors for treating radiation-induced hematopoietic injury might be more effective than other diseases without DNA repair.
ABSTRACT
The efficacy of rhIL-11 in treating thrombocytopenia and neutropenia in gamma-irradiated rhesus monkeys and the variation in curative effect due to difference of administration times were studied. Healthy rhesus monkeys were exposed to 3.0 Gy (60)Co total body irradiation (TBI) to result in pancytopenia for three weeks. Treatment with rhIL-11 (30, 60 or 120 micro g.kg(-1).day(-1)) on early days (days 0 - 13 after TBI) could significantly improve the nadir of platelet count. Although the nadir of leukocyte count was not improved, the duration below 50% of its baseline value was shortened similarly to that of platelet. During the first two weeks after TBI, erythrocyte numbers of the animals treated with these doses of rhIL-11 were lower than those of the control group at first but they became higher beginning from the third week. Four monkeys were treated with rhIL-11 at 60 micro g.kg(-1).day(-1) on days 13 - 26 after TBI. The numbers of their peripheral blood cells followed the similar decrease patterns as those of control group during the first three weeks, then they were improved rapidly. By semi-solid bone marrow cell culture it was demonstrated that rhIL-11 could stimulate bone marrow cells to form more CFU-Meg, CFU-Mix, CFU-E, BFU-E and CFU-GM in vitro. Histopathological observation revealed that bone marrow of the control group was devoid of hematopoietic cells and bleeding, being contrary to that of the group treated with rhIL-11, in which the cells proliferated actively. The results suggest that rhIL-11 can accelerate hematopoietic recovery of irradiated monkeys.