淸熱大補湯의 免疫調節作用을 通한 抗腫瘍效果

閔渶奎,金聖勳,金東熙 대한동의병리학회 2000 동의생리병리학회지 Vol.14 No.2

癌의 發生이 人體의 投病能力이 低下된 狀態에서는 免疫防禦機能이 弱化도어 癌細胞化된 非正常細胞를 破壞 除去하지 못하게 되어 細胞調節機能을 읽고 增殖하게 되는 것으로 認識되고 있고, 韓醫學에서도 癌의 病機를 正氣先虛· 留滯客邪·氣滯血瘀·邪毒積聚·成塊所形成의 機轉으로 形成되는 것으로 認識하고 있어, 免疫調節作用을 通한 抗癌作用에 대한 硏究가 最近 多樣하게 이루어지고 있다. 本 實驗에서는 淸熱大補湯의 免疫調節作用을 통한 抗腫瘍效果를 探索하기 위하여 多樣한 cytokine(IL-2,,4, 6, 12(p40,35), 18, interferon-γ)과 關聯된 免疫細胞(T.TH cell) 活性能 등을 檢索한 結果, 有意性있는 結果를 얻었다. This study was done to evaluate the immunomodulatory and antitumor effects of QingReDaBuTang(QRDBT). QRDBT significantly enhanced the lymphocyte proliferation through 3H thymidine uptake and also increased T helper cell up to 47% at 100 ug/ml. It downregulated IL-6 and IL-18, while it upregulated Il-2, IL-12(p35), IL-4- and in INF-γ. NO and carbon clearance were significantly increasey by QRDBT. These results indicate QRDBT exert antitumor activity by immunomodulation of cytokines.

황기도홍탕의 抗腫瘍 效果 및 免疫調節反應에 관한 硏究

鄭遇悅,李鎭弘,田炳熏 대한동의병리학회 1996 동의생리병리학회지 Vol.10 No.1

황기도홍탕의 抗腫瘍 효과 및 면역조절작용을 입증하고자 MCA로 腫瘍을 유발하고 leukemia cell line인 3LL 세포와 sarcoma cell line인 S-180 세포 및 FsaⅡ 세포를 마우스의 背部 皮下에 이식함으로써 발생되는 腫瘍의 發生率 및 크기등을 평가하고, 동시에 생체내 免疫過敏性 반응인 Arthus 반응 및 DTH반응, 그리고 抗體 生産能, 시험관내 NK세포의 활성도, 정상림프구와 mitogen으로 자극한 癌腫細胞의 增殖 반응, 림프구의 lymophokine 生産能등을 관찰하여 다음과 같은 결과를 얻었다. 황기도홍탕 추출액은 MCA로 유도한 腫瘍의 발생률과 크기를 감소시켰고, 3LL 세포 및 s-180세포 이식에 의한 腫瘍 발생을 감소시켰으나, Fsall 세포 이식에 의한 腫瘍발생에서는 영향을 미치지 못하였다. 또한 황기도홍탕 추출액은 시험관내 A431 세포의 증식에는 영향을 미치지 못하였으나, Fsall 세포의 增殖든 도리어 항진시켰고, 3LL 세포 및 S180 세포의 增殖은 저하시켰다. 황기도홍탕 추출액은 NK세포의 활성도를 증가시켰으며, 면역적혈구에 대한 마우스의 Arthus 반응 및 DTH 반응, 그리고 赤血球 凝集素의 免疫 반응들을 모두 항진시켰다. 황기도홍탕 추출액은 mitogen자극 램프구의 增殖能을 항진시켰으며 그 항진은 mitogen으로 세포를 자극함과 동시에 황기도홍탕 추출액에 노출시켰을 때 더욱 항진되었다. 황기도홍탕 추출액은 림프구의 IL-2 및 MIF 生産能에서는 영향을 미치지 못하였다. 이상의 결과로 보면 황기도홍탕의 종양효과와 면역조절반응은 MCA와 3LL 세포 및 S-180 세포로 유도된 皮下癌腫 세포에 대하여 특이적 細胞 毒性과 免疫調節作用에 의한 것으로 볼 수 있다. This study was carried out to evaluate the possible therapeutic or antitumoral effects of Hoangkidohongtang extract against tumor. and to carry out immunomodulatory effect. Some kinds of tumor were induced by the typical application of 3-methylcholanthrene(MCA) or by the implantation(s.c) of malignant tumor cells such as leukemia cells(3LL cells) or sarcoma cells(S-180 and Fasll cells). Treatment of the Hoangkidohongtang extract (daily 1 mg/mouse, i. p.) was continued for 7 days prior tumor induction and after that the treatment was lasted for 20 days. Against squamous cell carcinoma induced by MCA, Hoangkidohongtang decreased not only the frequency of tumor production but also the numbers and the weight of tumors per tumor bearing mice (TBM). Hoangkidohongtang also significantly suppressed the development of 3LL cell and S-180 cell by frequency and their size, and some developed tumors were regressed by the continuous treatment of Hoangkidohongtang extract into TBM. However, when tumor was induced by Fsall cell implantation, the growth of implanted cells in mice was delayed by the water extract of Hoangkidohongtang until day 7 and then rapid growth ensued. in vitro, treatment of Hoangkidohongtang extract had no effect on the growth of some kind of cell lines such as Fsall, A431 strain but significantly inhibited the proliferation of 3LL, S-180 cells. Hoangkidohongtang also stimulated the migrative ability of leucocyte, the MIF and IL2-production of T lymphocytes, but not IL6 production of B cells. Hoangkidohongtang enhanced Arthus reaction and DTH to sheep erythrocytes, and NK cells activities. These results demonstrated that Hoangkidohongtang extract exhibited a significant prophylatic benefits against tumors and showed different results according to the type of tumor cells. And these results also suggested that antitumor effect of Hoangkidohongtang might be chiefly due to nonspecific enhancement of NK cell activities and cell-mediated immune responses.

膈下逐瘀湯과 膈下逐瘀湯合四君子湯의 抗癌 및 免疫調節作用에 關한 實驗的 硏究

崔昇勳,安圭錫,文濬典,高光錫 대한동의병리학회 1994 동의생리병리학회지 Vol.9 No.1

연구배경 : 암은 사망의 주요 원인이 되는 질환으로 매년 증가하고 있는 추세이다. 이에 mouse에 암을 유발하여, 약물치료를 시행함으로써 높은 치료효과를 거두는 한약제재를 개발하여 암의 치료에 기여하고 아울러 근본적인 예방치료에 대한 새로운 방법을 제시하고자 함. 방법 : 생쥐에 Sacroma 180을 이식하여 복강암을 유발하고 격하축어탕 및 격하축어탕합사군자탕을 투여하여 생명연장률과 B cell 및 T cell, 혈청항체가, 임파구증식반응, IL-2 생산능 및 자연살해페소의 활성도를 측정하였다. 결과 : 격하축어탕과 격하축어탕합사군자탕은 면역조절작용을 통한 항암효과가 있을 것으로 생각되며, 활혈거어제인 격하축어탕과 보기제인 사군자탕을 합방했을때, 그 효과가 증가되었다. In order to investigate the effects of Gyeokhachukeotang and Gyeokhachukeotang plus Sagunjatang on anti-tumor and immunodulatory reaction to the ICR and C57BL/6 mice which have abdominal tumor after Sarcoma-180 cells were transplanted, the extracts of herbal medicines above mentioned were orally administered to the mice for 21 days to observe the extention of survival duration of the mice, quantitation of T cells and B cells, productivitiy of interleukin-2, lymphocytes transformation, hemagglutinin titer and hemolysin titer and activity of splenic natural killer cells. The results are summarized as follows; 1. In the effect of life extention, the Gyeokhachukeotang-medicated mice group inclined to show extended duration of life, which is of no great significant difference and the mice group medicated with mixture of Gyeokhachukeotang plus Sagunjatang appeared to survive longer than the Gyeokhachukeotang-medicated mice group, which is not meaningful. 2. Considering T cell and B cell content, the Gyeokhachukeotang-medicated mice group had a meaningful increase in B cell (P<0.05) content, and the mice group medicated with the mixture of Gyeokhachukeotang plus Sagunjatang remarkably showed a significant increase in both T cell and B cell (P<0.01). 3. Considering serum antibody titer tended to increase in case of the Gyeokhachukeotang-medicated mice group, which is of no significant difference, while decreasing in case of the mice group medicated with mixture of Gyeokhachukeotang plus Sagunjatang. 4. In lymphocyte transformation marked a significant increase the Gyeokhachukeotang-medicated mice group, marked a significant (P<0.01), and remarkably showed a significant increase the mice group medicated with the mixture of Gyeokhachukeotang plus Sagunjatang (P<0.001). 5. As for the productivity of interleukin-2 and the activity of NK cells, the both tested groups inclined to show an increase or a decrese, but there is no significance.

韓醫學的 診斷類型에 따른 韓藥方劑의 抗癌 및 免疫調節作用에 미치는 影響

朴鐘鉉,金楨氾,崔昇勳,安圭錫 대한동의병리학회 1994 동의생리병리학회지 Vol.9 No.1

연구배경 : 암은 사망의 주요한 원인이 되는 질환으로서, 우리나라에 있어서도 급격히 증가하는 추세이다. 한의학에서는 암의 유형을 크게 간울기체형, 기체혈어형, 비허습담형, 음허내열형 등으로 분류하고 있는데, 각 유형에 응용할 수 있는 소요산, 소복축어탕, 사군자탕, 육미지황탕의 항암효능을 비교 연구함으로써, 암치료에 대한 한약재의 임상활용도를 높이고자 함. 방법 : Mouse에 Sarcoma-180으로 복강암을 유발한 후, 약제를 21일 간 투여하고 생존율, T cell, B cell, 혈청항체가, IL-2 생산능, NK cell의 세포살상능을 측정하였다. 결과 : 생존기간의 연장효과는 모든군에서 증가하는 경향이 있었으나 유의성이 없었고, T cell 및 B cell은 모든군에서 증가하였으며, 임파구 증식반응 및 IL-2 생산능은 사군자탕과 육미지황탕에서, NK cell 활성도는 소복축어탕 엑기스 투여군에서 유의성이 있었다. 결론 : 이상으로 보아 이들 처방은 면역조절작용을 통한 항암효과가 있을 것으로 볼 수 있으며, 변증분형에 따라 처방을 달리해야 함을 알 수 있다. In order to investigate the effects of Formules according to Pattern Identification on anti-tumor and immunodulatory reaction to the ICR and C57BL/6 mice which have abdominal tumor after Sarcoma-180 cells were transplanted, the extracts of herbal medicines above mentioned were orally administered to the mice for 21 days to observe the extention of survial duration of the mice, quantitation of T cells and B cells, productivity of interleukin-2, lymphocytes transformation, hemagglutinin titer and hemolysin titer and activity of splenic natural killer cells. The results are summarized as follows ; 1. In the effect of life extention, all groups appeared to survive longer than the Control group, which are not meaningful. 2. Considering T cell and B cell content, all groups had a meaningful increase in both T cell and B cell (P<0.01). 3. Considering serum antibody titer was no significant difference between all groups. 4. In lymphocyte transformation marked a significant increase the sijunzitang-medicated mice group, marked a significant (P<0.01), and showed a significant increase the mice group medicated with Liuweidihuangtang (P<0.05). 5. As for the productivity of interleukin-2, showed a significant increase the mice group medicated with Sijunzitang ans Liuweidihuangtang (P<0.05). 6. In the effect of activity of NK cells, Shaofuzhuyutang-medicated mice group had a meaningful increase (P<0.05).

인간 재조합 인터루긴-32 면역조절작용에 대한 유세포 분석

이광수,김영관,채정일,심정현,김은미,강형식,김수현,윤도영,명평근 충남대학교 생물공학연구소 2006 생물공학연구지 Vol.12 No.-

Xenotransplantation of porcine organs has the potential to overcome the severe shortage of human tissues and organ available for human transplantation. however, it remains various hurdles for clinical xenotransplantation. In pig and mouse xenotransplantation, porcine xenograft evoke a strong cellular rejection response in immunocompetent host and grafts are destroyed within a week. This cellular immune response could involved both T cells and NK cells. A number of groups have shown that human NK cells can recognize and damage porcine endothelial cells. In addition, human T cells can respond to porcine endothelial cells through both direct and indirect mechanisms. Cellular rejection of porcine tissues requires T cells, particularly CD4^(+) cells. A new cytokine recombinant human interleukin-32α,β(IL-32α,β) has a role innate and acquired immune system. In order to investigate the role of recombinant mouse IL-18 and recombinant human IL-32α,β in xenograft rejection, we transplanted the PK(15) cells to C57BL/6 mice with or without intraperitoneal injection of recombinant mouse IL-18 or recombinant human IL-32 α,β. It was analyzed the population of NK cell, T cell and B cell in the C57BL/6 mice transplanted with PK(15) cells and recombinant mouse IL-18 or recombinant human IL-32α,β by flow cytometry analysis. As a result, lymph node and thymus of PK15/IL18, PK15/IL32α and PK15/IL32β injected group were increased to T cell activation population than normal injected groups. CD8^(+) T cells were decreased in lymph node of PK15/IL18, PK15/IL32α and PK15/IL32β injected groups. CD4^(+) T cells were increased in lymph node cell of PK15/IL32α and PK15/IL32β injected group and also, B cell population were increased in lymph node cell and spleen of PK15/IL18, PK15/IL32α and PK15/IL32β injected group. Therefore, we suggest that recombinant mouse IL-18 and recombinant human IL-32α,β suppress xenograft rejection in cellular xenotransplantation.