Kitahara M, Kishimoto S, Hirano T, Kishimoto T, Okada M
Department of Medicine, Osaka University Hospital.
Jpn J Cancer Res. 1990 Oct;81(10):1032-8. doi: 10.1111/j.1349-7006.1990.tb03342.x.
Administration of recombinant interleukin-6 (IL-6) was found to induce in vivo generation of cytotoxic T lymphocytes (CTL) against syngeneic transplantable erythroleukemia (FBL-3) in lymph node cells and peritoneal exudate cells (PEC) in C57BL/6 mice. Furthermore, 15 out of 16 C57BL/6 mice injected with 5 x 10(6) viable FBL-3 cells survived on day 100 when they were treated with 5 x 10(4) U of recombinant IL-6 three times a day on days 1, 2, 3, 5, 7 and 9 after the inoculation of tumor cells (the cure rate was 94%). Cured mice could reject the tumor cells rapidly after the re-inoculation of a large number of live FBL-3 cells. In contrast, all normal mice died of tumor development by day 10. In these cured mice, FBL-3-specific CD4-8+ CTL cells were found to be generated in PEC, spleen and lymph node cells by either in vivo or in vitro re-stimulation with FBL-3 cells, but lymphokine-activated killer cells never developed. The results suggested that the anti-tumor effect of IL-6 was mediated by in vivo induction of tumor-specific CTL.
研究发现,给予重组白细胞介素-6(IL-6)可在C57BL/6小鼠的淋巴结细胞和腹腔渗出细胞(PEC)中诱导针对同基因可移植性红白血病(FBL-3)的细胞毒性T淋巴细胞(CTL)在体内生成。此外,在接种肿瘤细胞后的第1、2、3、5、7和9天,每天3次给予5×10⁴U重组IL-6进行治疗时,16只注射了5×10⁶个活FBL-3细胞的C57BL/6小鼠中有15只在第100天存活(治愈率为94%)。治愈的小鼠在再次接种大量活FBL-3细胞后能够迅速排斥肿瘤细胞。相比之下,所有正常小鼠在第10天时均因肿瘤发展而死亡。在这些治愈的小鼠中,通过用FBL-3细胞进行体内或体外再刺激,发现PEC、脾脏和淋巴结细胞中产生了FBL-3特异性CD4⁻8⁺CTL细胞,但从未产生过淋巴因子激活的杀伤细胞。结果表明,IL-6的抗肿瘤作用是由体内诱导肿瘤特异性CTL介导的。