## 4 Discussion
Based on the 13 hematological test results in this study, significant reductions were observed in the total leukocyte and RBC count, HGB, HCT, and platelet count of the CPA control group compared to those in the control group. Moreover, as a result of panekukopenia, no change was observed in the leukocyte differential count in this experiment. In contrast, the decrease in total leukocyte and RBC count, HGB, HCT, and platelet count due to hematopoietic inhibition by CPA administration was significantly suppressed in a dose-dependent manner by the oral administration of AR (100, 200, and 400 mg/kg). In particular, AR at a dose of 100 mg/kg showed a reduction in the inhibition of the hematopoietic system, comparable to that of 200 mg/kg of EAP. These results suggest that oral administration of AR (100, 200, and 400 mg/kg), at least under the hematological examination conditions of this study, inhibits CPA-induced pankulopenia, thrombocytopenia, and aplastic anemia in a dose-dependent manner. This is regarded as reliable evidence, showing an inhibitory effect at a 100 mg/kg oral dose of AR as compared to EAP (200 mg/kg). TNF-\(\alpha\) is a representative cytokine produced in various types of cells, including splenocytes, and plays an important role in the differentiation of T lymphocytes [52]. TNF-\(\alpha\) generally activates cellular immunity and increases the function of IL-2, which promotes antibody production [52, 53]. IL-1 is another type of cytokine secreted by various cells, such as macrophages, dendritic cells, lymphocytes, endothelial cells, fibroblasts, and keratinocytes. There are two types of IL-1: cell-secreted IL-1\(\beta\) and membrane-attached IL-1\(\alpha\). IL-1 plays an important role in the immune response [54]. IL-6 is secreted by Th2 cells and macrophages accompanying trauma, such as burns that cause inflammation owing to various infections and damage to surrounding tissues [55] and plays an important role against various bacteria [56]. IL-12 is produced and secreted in response to antigen stimulation in dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells [57]. The secreted IL-12 promotes Th1 cell differentiation through stimulation of IFN-\(\gamma\) and TNF-\(\alpha\) secretion. In addition, IFN-\(\gamma\) is secreted by CD8+ T lymphocytes, Th1 cells, and NK cells, and affects the functions of B- and T-cells and enhances the functions of NK cells and macrophages [53, 54]. CPA is a typical immunosuppressant that mainly suppresses the secretion of various cytokines by significantly reducing the number of T lymphocytes [11, 13, 16, 30]. In this study, the IFN-\(\gamma\), TNF-\(\alpha\), IL-1\(\beta\), IL-6, and IL-12 content in blood and spleen tissue were significantly reduced. Reduction in IL-6 and IL-12 mRNA expression were induced by CPA administration. However, in the AR (100, 200, and 400 mg/kg) administered groups, the levels of IFN-\(\gamma\), TNF-\(\alpha\), IL-1\(\beta\), IL-6, and IL-12 in the blood and spleen tissues were significantly higher than those in the CPA control group, and the IFN. Increases in the mRNA expression of IFN-\(\gamma\), TNF-\(\alpha\), IL-1\(\beta\), IL-6, and IL-12 were confirmed in a dose-dependent manner. In particular, AR at a dose of 100 mg/kg showed an inhibitory effect on the reduction in cytokine content and mRNA expression in CPA-induced blood and spleen tissue, comparable to that of EAP (200 mg/kg). These results, at least under the conditions of this study, provide convincing evidence that oral administration of AR (100, 200, and 400 mg/kg) significantly suppresses the CPA-induced decrease in cytokine production and expression by CPA in a dose-dependent manner, showing a suppressing effect comparable to EAP (200 mg/kg) at 100 mg/kg oral dose of AR. As part of the immunosuppression by CPA, the function of immune-responsive cells, such as NK cells and macrophages, is significantly suppressed, and the activity of these immune-responsive cells is currently in the limelight as another concept of immune modulator development [58, 59].