化疗药物体内外对免疫活性细胞的影响

Influence of Chemotherapeutic Drugs on Immunocytes in vitro and in vivo

目的 :通过化疗对机体免疫细胞影响的研究 ,探讨肿瘤化疗后衔接生物治疗的最佳时效。方法 :采用细胞培养技术 ,观察化疗药物对培养的肿瘤细胞、小鼠腹腔巨噬细胞和脾淋巴细胞的毒性作用 ;同时还观察化疗药物作用小鼠体内不同时间后 ,其对小鼠腹腔巨噬细胞和脾淋巴细胞代谢和激活功能的影响 ;运用细胞计数的方法 ,观察化疗对小鼠腹腔巨噬细胞和外周血免疫细胞的动力学影响 ;另外对经化疗药物注射 2d后的小鼠进行H2 2肝癌细胞接种 ,14d后解剖小鼠观察肿瘤生长。结果 :化疗药物体外对免疫细胞有很强毒性作用 ,体内使免疫细胞代谢降低 ,活化受阻 ,并使免疫细胞动力学发生改变 ,在化疗后第 3天免疫细胞数降至最低 ,约 10d左右恢复正常 ;化疗药物注射小鼠体内 2d后 ,再接种瘤细胞 ,肿瘤生长明显加快。结论 :化疗既降低机体免疫细胞数量 ,又抑制其功能 ,且在其杀瘤作用消失后还具有间接促瘤生长的作用 ,因此 ,化疗后立即实施以肿瘤免疫治疗为主的生物治疗是不恰当的 ,在化疗后间隔较长时间再给予生物治疗也是不恰当的 ,生物治疗应选择在化疗药物作用消失后 ,免疫细胞数降至最低或开始恢复时实施 ,方能取得较好的效果。

Objective: To invistigate the relationship between time and efficacy of the linkage of tumor biotherapy after chemotherapy by studying the influence of chemotherapeutic drugs on immunocytes.Methods: The cytotoxicity of chemotherapeutic drugs to tumor cells, mouse peritoneal macrophages and spleen lymphocytes was observed by cell culture technique. The influence of chemotherapeutic drugs to the metabolism and activation of macrophages and lymphocytes at different time after peritoneal injection of drugs was observed. The mice were inoculated with tumor cells two days after the injection of drugs, and the growth of tumor was measured 14 days after inoculation by anatomizing mice. Results: Chemotherapeutic drugs had cytotoxicity in vitro to different cells, suppressed the function of immunocytes, and decreased the number of immunocytes in vivo. After injection of drugs, the number of immunocytes was the lowest on the third day and recovered to the nomal level on the 10th day. If drugs was injected two days before the inoculation of tumor cells, the growth of tumor became faster than control group. Conclusions: Chemotherapy not only decreases the number of immunocytes but also suppresses the function of immunocytes, and it can promote the growth of tumor after its cytotoxicity disappeared. So it is not good that biotherapy, which depends on immunocyte to kill tumor cells, is used immediately after chemotherapy and it is also not good for using biotherapy with a long interval after chemotherapy . It is good time to use biotherapy when the number of immunocytes is lowest or the recovery just starts.