Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model
Th2/Th1 switch induced by a single low dose of cyclophosphamide in a rat metastatic lymphoma model
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DOI：
10.1007/s00262-001-0237-3
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发表时间：
2002-01-01
影响因子：
5.8
通讯作者：
Scharovsky, OG
中科院分区：
文献类型：
--
作者：
Matar, P;Rozados, VR;Scharovsky, OG
环磷酰胺（Cyclophosphamide，Cy）是一种广泛应用于肿瘤化疗的烷化剂。它对免疫系统有双峰效应。这取决于给药的剂量和时间表。我们以前已经证明，单次低剂量的Cy具有抗代谢抑制作用。通过免疫调节，在淋巴瘤大鼠中实现。这样的治疗减少了IL-10的脾脏产生。TGF-β和NO，恢复淋巴增殖能力。低剂量Cy处理诱导的从免疫抑制到免疫增强的转变主要由IL-10产生的减少介导。本研究集中于分析通过用单次低剂量Cy治疗对1型细胞因子水平的调节以及这些细胞因子（IL-2和IFN-γ）和IL-10对原发性肿瘤和转移性细胞生长的影响。我们的研究结果表明，一个单一的低剂量的Cy诱导淋巴瘤大鼠的细胞因子谱中的Th 2/Th 1的转变。这可能是其抗转移作用的原因。还显示了作为生长因子的IL-10和作为细胞毒性因子的IFN-γ对转移性细胞的直接作用。
Cyclophosphamide (Cy) is an alkylating agent widely used in cancer chemotherapy. It has a bimodal effect on the immune system. depending on the dose and schedule of administration. We have previously demonstrated that a single low dose of Cy has an antimet-astatic effect. achieved through immunomodulation, in lymphoma bearing rats. Such a treatment reduced the splenic production of IL-10. TGF-beta, and NO, restoring the lymphoproliferative capacity. A shift from immunosuppression to immunopotentiation induced by low-dose Cy treatment was mainly mediated by a decrease in IL-10 production. The present study focused on the analysis of the modulation of type-1 cytokine levels by treatment with a single low dose of Cy and the effect these cytokines (IL-2 and IFN-gamma) and IL-10 have on primary tumor and metastatic cell growth. Our results suggest that a single low dose of Cy induces a Th2/Th1 shift in the cytokine profile of lymphoma-bearing rats. which may be responsible for its antimetastatic effect. A direct action of IL-10 as a growth factor and IFN-gamma as a cytotoxic factor on metastatic cells is also shown.