Enhancement of Repopulation and Hematopoiesis of Bone Marrow Cells in Irradiated Mice by Oral Administration of PG101,a Water-Soluble Extract from Lentinus lepideus

Abstract

PG101 is a water-soluble extract from Lentinus lepideus. It is a potential biological response modifier that activates selective cytokines in vitro, mainly by controlling cellular transcription factor NF-κB. Effects of PG101 were tested on bone marrow cells in irradiated mice. Mice were irradiated with a dose of 6 Gy and were given PG101 by gavages daily for 24 days. In PG101-treated mice, the number of colony-forming cells, including colony-forming units (CFU)-granulocytes/macrophages (GM) and erythroid burst-forming units (BFU-E), were increased to almost the levels seen in nonirradiated control as early as 8 days after irradiation. Two-color flow cytometric analysis using antibodies to ER-MP12 and ER-MP20 suggested that in the bone marrow cell population, PG101 increased the number of granulocytes (ER-MP12^-20^med) and myeloid progenitors (ER-MP12⁺20⁺). Analysis of surface c-Kit and Gr-1 proteins in bone marrow cells indicated that PG101 might induce differentiation of progenitor cells to granulocytes and/or proliferation of the committed cells. Lastly, oral administration of PG101 highly increased serum levels of GM-CSF, IL-6, and IL-1β. Interestingly, the level of TNF-α was elevated by irradiation in control mice, but was maintained at the background level in PG101-treated mice, suggesting that PG101 might effectively suppress TNF-α-related pathologic conditions. Our results strongly suggest the great potential of PG101 as an immune enhancer during radiotherapy and/or chemotherapy.