Traditional Chinese medicine compound, Bu Sheng Hui Yang Fang, promotes the proliferation of lymphocytes in the immunosuppressed mice potentially by upregulating IL-4 signaling
Traditional Chinese medicine compound, Bu Sheng Hui Yang Fang, promotes the proliferation of lymphocytes in the immunosuppressed mice potentially by upregulating IL-4 signaling
复制标题
中药复方补生回阳方可能通过上调 IL-4 信号传导促进免疫抑制小鼠淋巴细胞增殖
DOI：
10.1016/j.biopha.2020.111107
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发表时间：
2021-02-01
影响因子：
7.5
通讯作者：
Yang, Tonghua
中科院分区：
文献类型：
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作者：
Wang, Yajie;Tan, Jiabin;Yang, Tonghua
在恶性疾病的发生和发展过程中，免疫系统在预防感染和癌症免疫监控中起着关键作用。由于化疗方案中的细胞毒剂和免疫抑制糖皮质激素，癌症患者往往免疫功能低下，容易发生难治性感染和白血病复发。补肾回阳方是一种传统的中药复方，在中国中被广泛用于增强白血病患者的免疫系统，并结合化疗有效降低其感染风险，但其具体作用机制尚不清楚。因此，我们利用免疫抑制的小鼠模型研究了补肾益气汤对免疫系统的影响。通过对氢化可的松诱导的免疫抑制BALB/C小鼠免疫系统的分析，发现补肾益气饮治疗后小鼠脾中的CD4(+)和CD8(+)淋巴细胞明显增加。此外，我们还发现补肾益气汤治疗组免疫系统的增强是由于淋巴细胞增殖增加和凋亡减少所致。细胞因子阵列分析显示，免疫抑制小鼠血浆中的白介素4(IL-4)降低，但经补肾益气饮治疗后恢复到正常水平。此外，我们还发现IL-4是急性髓系白血病患者的不良预后因子，补肾益气饮可使部分IL-4升高。在机制上，我们发现BSHY以一种STAT6依赖的方式促进淋巴细胞的增殖。综上所述，我们目前的研究表明，补肾益气饮通过上调IL-4信号，促进免疫抑制小鼠淋巴细胞的增殖。
The immune system plays a pivotal role in defending against infection and cancer immunosurveillance during the onset and procession of malignant disease. Cancer patients are frequently immunocompromised and subject to refractory infection and relapse of leukemia, due to the cytotoxic agents and immunosuppressive glucocorticoids in the chemotherapy regimens. Bu Shen Hui Yang Fang (BSHY), a traditional Chinese compound, was widely used in China to enhance the immune system of leukemia patients combined with chemotherapy and effectively lowered their risk of infection, with specific mechanism unknown yet. Thus, we investigated the effects of BSHY on the immune system using immunosuppressive mouse models. By analyzing the immune system of immuno-suppressed BALB/C mice induced by hydrocortisone, we found an increase of CD4(+) and CD8(+) lymphocytes in the spleens of mice after BSHY treatment. Furthermore, we found the enhanced immune system in BSHY treated group was due to increased proliferation and decreased apoptosis of lymphocytes. Cytokine array analysis revealed that interleukin 4 (IL-4) was reduced in the plasma of immunosuppressed mice but returned to a normal level after BSHY treatment. Moreover, we found IL-4 was an adverse prognostic factor in acute myeloid leukemia patients and part of them could be elevated by BSHY. Mechanistically, we found BSHY enhances the proliferation of lymphocytes in a Stat6-dependent manner. In summary, our current study demonstrates that BSHY enhances the proliferation of lymphocytes in the immunosuppressed mice via upregulating IL-4 signaling.