Matar Pablo, Rozados Viviana R, Gervasoni Silvia I, Scharovsky Graciela O
Instituto de Genética Experimental, Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Santa Fe 3100, (2000) Rosario, Argentina.
Cancer Immunol Immunother. 2002 Jan;50(11):588-96. doi: 10.1007/s00262-001-0237-3. Epub 2001 Nov 16.
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 antimetastatic 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.
环磷酰胺（Cy）是一种广泛用于癌症化疗的烷化剂。根据给药剂量和方案，它对免疫系统有双峰效应。我们之前已经证明，单次低剂量的Cy在荷淋巴瘤大鼠中通过免疫调节具有抗转移作用。这种治疗降低了脾脏中IL-10、TGF-β和NO的产生，恢复了淋巴细胞增殖能力。低剂量Cy治疗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。本研究重点分析单次低剂量Cy治疗对1型细胞因子水平的调节作用，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细胞生长的影响。我们的结果表明，单次低剂量的Cy在荷淋巴瘤大鼠的细胞因子谱中诱导了Th2/Th1转变，这可能是其抗转移作用的原因。还显示了IL-10作为生长因子和IFN-γ作为细胞毒性因子对转移细胞的直接作用。
