白细胞介素6抗肿瘤作用的实验研究

Experimental Study on the Anti-tumor Mechanism of Interleukin-6

用S180腹水瘤动物模型,经IL-6治疗后绝大多数肿瘤消退(8/10),且用同一肿瘤再次攻击不能生长,对照组中大多数小鼠因肿瘤进展而死亡(9/10).经S180肉瘤再次攻击的动物脾脏明显肿大,约为对照组的4倍以上,镜下观察脾脏白髓明显增生,牌中央动脉周围淋巴鞘明显增大,主要由大淋巴细胞及免疫母细胞构成,与薄层小淋巴细胞构成的边缘区分界明显,而脾小结的淋巴滤泡亦可见明显的生发中心.体外细胞毒测定显示:实验组脾细胞对S180靶细胞的杀伤作用明显高于对照组(907±318:387±144,P=0.003).对L929靶细胞的细胞毒亦是如此(1145±164:186±251,P<0.001).提示IL-6在活体内可激发荷瘤宿主对肿瘤的免疫反应.体外经IL-6处理的人PBL及人瘤靶细胞,亦明显增强效应细胞的杀伤活性.有趣的是这一现象主要是肿瘤细胞对效应细胞的杀伤敏感性增加,其机制可能是通过增强细胞间识别分子表达,诱发效应细胞对肿瘤的免疫应答来实现.

Segregated Kunming mice bearing S180 sarcoma were used as tumor models and treated with rhIL-6. The tumor regressed in most of the treated mice (8/10) in which there was no tumor growth when rechallenged with the same tumor cells, whereas 9/10 of controls died as the tumor progressed. Morphologically, in the treated group, the mice had enlarged spleen (4 times larger than that of control group)with hyperplastic white pulp consisted predominantly of activated lymphocytes. Cytotoxicity of spleen cells from IL-6 treated group to autologous tumor cells was higher than that of control group (907 ±318: 387 ±144, P=0.003) and so did L929 cell line used as target (1145±164: 186±251).We also set in vitro experiment using human PBL and human melanoma and colon carcinoma cell lines (A375,LS174). These cells were treated with IL-6 respectively and the cytotoxicity was assayed. Although PBL stimulated with IL-6 killed the LS174 more efficiently,the higher cytotoxicity to LS174 is because of the increased sensitivty of LS174 to the effector cells .On the contrary,IL-6 showed no effect on the A 375 cell line. It is assumed that this difference might result from the discrepancy of the recognition molecules existed on the cell surface between these two cell lines.