We previously reported that ginsan, a purified polysaccharide isolated from Panax ginseng, had a mitogenic activity, induced LAK cells, and increased levels of several cytokines. In an effort to identify other immunostimulatory effects, we evaluated the protective effects of ginsan injected in vivo against radiation by measuring its effects on the CFU-S bone marrow cells and spleen cells. Ginsan was found to significantly increase the number of bone marrow cells, spleen cells, granulocyte-macrophage colony-forming cells (GM-CFC), and circulating neutrophils, lymphocytes and platelets in irradiated mice. In addition, ginsan induced the endogenous production of cytokines such as Il1, Il6, Ifng and Il12, which are required for hematopoietic recovery, and was able to enhance Th1 function while interfering with the Th2 response in irradiated mice. We demonstrated that pretreatment with ginsan protected mice from the lethal effects of ionizing radiation more effectively than when it was given immediately after or at various times after irradiation. A significant increase in the LD(50/30) from 7.54 Gy for PBS injection to 10.93 Gy for mice pretreated with 100 mg/kg ginsan was observed. These findings indicate that ginsan may be a useful agent to reduce the time necessary for reconstituting hematopoietic cells after irradiation.
These results suggest that gamma irradiation may play a role in Th1 and Th2 cytokine expression, via regulation of the level of cytokine-mediators through transcriptional modulation and Stat signaling. These results are helpful to understand general profile of cytokine expression in response to gamma irradiation.
Gamma radiation causes suppression of the immune function, and immune properties are related to cytokine production. In the present study, the polysaccharide, Ginsan, purified from an ethanol-insoluble fraction of Ginseng (Panax ginseng C.A. Meyer, Araliaceae) water extract was studied to assess its effects on the immunosuppressive activities of gamma radiation. Ginsan was found to stimulate murine normal splenocytes by inducing the mRNA expressions of Th1 and Th2 type cytokines, and also restore the mRNA expression of IFN-gamma, Th1 cytokine, after its inhibition by whole-body gamma irradiation. Therefore, Ginsan was found to restore the T lymphocytes function that had been suppressed by gamma irradiation in allogenic MLR (mixed lymphocyte reactions). However, Ginsan exhibited no excessive stimulatory effects on the control group. The above results indicated that Ginsan may constitute a new noble agent for the improvement of gamma radiation-induced immunosuppression.
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