Down regulation of T-cell-derived IL-10 production by low-dose cyclophosphamide treatment in tumor-bearing rats restores in vitro normal lymphoproliferative response
Down regulation of T-cell-derived IL-10 production by low-dose cyclophosphamide treatment in tumor-bearing rats restores in vitro normal lymphoproliferative response
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DOI：
10.1016/s1567-5769(00)00028-x
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发表时间：
2001-02-01
影响因子：
5.6
通讯作者：
Scharovsky, OG
中科院分区：
文献类型：
--
作者：
Matar, P;Rozados, VR;Scharovsky, OG
在以前的报告中，我们证明了一个单一的低剂量的环磷酰胺（Cy）对自发和实验性转移的大鼠淋巴瘤（L-TACB）的抑制作用。这种抗转移作用可以通过免疫脾细胞从Cy-treated Turner轴承大鼠过继转移，它被废除通过使用免疫抑制主机，这表明免疫调节作用。随后，我们发现TGF-β、IL-10和NO水平的升高通过抑制淋巴细胞增殖参与肿瘤诱导的免疫抑制。用低剂量Cy治疗荷瘤大鼠减少了脾脏这些抑制性细胞因子的产生，恢复了淋巴增殖能力，否则在肿瘤生长期间会减弱;th.在这里，我们研究了由Cy治疗调节的细胞因子的变化，这些细胞因子负责淋巴增殖反应的恢复，并在我们的实验模型中确定了产生TGF-β、IL-10和NO的脾细胞类型。我们目前的研究结果表明，IL-10和NO是专门由T淋巴细胞和巨噬细胞，分别产生，而TGF-β是由这两种细胞类型。荷瘤大鼠T细胞产生的高水平IL-10是抑制淋巴细胞增殖的原因。此外，我们的研究结果表明，从免疫抑制到免疫增强的转变，由单次低剂量的Cy治疗荷瘤大鼠诱导的T细胞衍生的IL-10产生的减少介导的，这将占，在相同程度上，为Cy治疗的抗转移作用。(C)2001 Elsevier Science B. V.保留所有权利。
In previous reports, we demonstrated an inhibitory effect of a single low-dose of cyclophosphamide (Cy) on spontaneous and experimental metastasis of a rat lymphoma (L-TACB). This antimetastatic effect could be adoptively transferred by immune spleen cells from Cy-treated turner-bearing rats and it was abrogated by the use of immunosuppressed hosts, suggesting an immunomodulatory effect. Subsequently, we found that increased levels of TGF-beta, IL-10 and NO were involved in tumor-induced immunosupression by inhibiting lymphocyte proliferation. The treatment of tumor-bearing rats with low-dose Cy reduced the splenic production of these suppressive cytokines, restoring the lymphoproliferative capacity otherwise diminished during tumor growth;th. Here, we investigated the changes of the cytokines modulated by the Cy therapy that are responsible for the restoration of the lymphoproliferative response and determined the spleen cell type producing TGF-beta, IL-10 and NO in our experimental model. Our current results show that IL-10 and NO are produced exclusively by T lymphocytes and macrophages, respectively, whereas TGF-beta is produced by both cell types. The high level of IL-10 produced by T-cells from tumor-bearing rats is responsible for the inhibition of lymphocyte proliferation. Moreover, our results suggest that the shift from immunosuppression to immunopotentiation induced by treatment of tumor-bearing rats with a single low-dose of Cy is mediated by a reduction in T-cell derived IL-10 production, which would account, to same extent, for the antimetastatic effect of Cy treatment. (C) 2001 Elsevier Science B.V. All rights reserved.