Direct Injection of Plasmid DNA Expressing IL-6 Gene Improves Recovery of Thrombocytopoiesis in Irradiated Mice / 中国实验血液学杂志

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.