Hematopoietic and lymphoid cell recovery from radiation damage by cytokines

Radiation therapy causes various degrees of damage to hematopoietic cells. Cepharanthine (CE), a plant alkaloid, showed the most prominent restorative effect on hematopoiesis among the antileukopenia drugs examined in a previous study. Its mechanism of action was further analyzed in this study, and the following results were obtained: Intravenous administration of CE every other day for 10 days after irradiation increased CFU-S two-fold. CE-conditioned medium from bone marrow stroma cells increased CFU-C. Higher concentrations of CE in the culture non-specifically suppressed the growth of various types of cells, including T cells. However, this suppression disappeared in the presence of peritoneal exudate macrophages (PEC). When Con A blasts were co-cultivated on PEC, concentrations between 10(-6) to 10(-12) M promoted growth of both PEC and T cells. 10 pg/ml and 8 pg/ml of IL-1 were produced from 10(6)/ml of PEC and bone marrow stroma cells, respectively, in 24 hrs with CE. A lesser amount was also produced from thymus stroma cells. A detectable amount of IL-6 was produced from CE-stimulated bone marrow stroma cells. These findings suggested that CE acted as a cytokine-inducer on various epithelial cells in the body and the cytokines thus produced stimulated multipotential hematopoietic progenitors and their progeny as growth and/or differentiation factors.