Nakashima Y, Mita S, Takatsu K, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Japan.
Cancer Immunol Immunother. 1993 Sep;37(4):227-32. doi: 10.1007/BF01518515.
The antitumor activity of peritoneal exudate cells (PEC) induced by murine interleukin-5 (mIL-5) was examined using Meth-A sarcoma cells transplanted into the peritoneal cavity of mice. Although in vitro treatment of Meth-A sarcoma cells with mIL-5 did not result in inhibition of their growth, treatment of mice intraperitoneally with mIL-5 (1 microgram/day) from day -5 to +5 (tumor cells were inoculated on day 0) led to a significant increase in survival or even rejection of tumor cells. This antitumor effect depended on the dose of mIL-5. Interestingly, there was identical therapeutic activity when the protocol of days -10 to -1 was used as opposed to -5 to +5. In addition, post-treatment with mIL-5 from day +1 to +10 was ineffective. This suggests that the therapeutic activity of IL-5 is largely prophylactic. Under the former condition, the number of PEC was found to increase over 50-fold when compared to levels in control mice. Moreover, the antitumor effect of mIL-5 was completely abolished by subcutaneous injection of anti-mIL-5 monoclonal antibodies. The treatment of mice injected intraperitoneally with human IL-2 also resulted in an increase in survival. Winn assay experiments using PEC recovered from mIL-5-treated mice (1 microgram/day, from day -10 to -1) revealed that these PEC could mediate antitumor activity against Meth-A sarcoma cells. Furthermore, when the cured mice were re-injected with Meth-A sarcoma cells or syngeneic MOPC104E cells, they could reject Meth-A sarcoma cells but not MOPC104E cells, indicating that immune memory had been generated. These results suggest that IL-5 augmented the PEC tumoricidal activity but we have no indication that the tumoricidal activity was mediated through a mIL-5-dependent mechanism.
利用接种于小鼠腹腔的Meth-A肉瘤细胞，检测了小鼠白细胞介素-5（mIL-5）诱导的腹腔渗出细胞（PEC）的抗肿瘤活性。虽然用mIL-5对Meth-A肉瘤细胞进行体外处理未导致其生长受到抑制，但从第-5天至+5天（肿瘤细胞于第0天接种）对小鼠进行腹腔内注射mIL-5（1微克/天），可导致生存率显著提高，甚至肿瘤细胞被排斥。这种抗肿瘤作用取决于mIL-5的剂量。有趣的是，与使用第-5天至+5天的方案相比，使用第-10天至-1天的方案具有相同的治疗活性。此外，从第+1天至+10天用mIL-5进行治疗后无效。这表明IL-5的治疗活性主要是预防性的。在前一种情况下，与对照小鼠相比，PEC的数量增加了50倍以上。此外，皮下注射抗mIL-5单克隆抗体可完全消除mIL-5的抗肿瘤作用。对腹腔内注射人IL-2的小鼠进行治疗也导致生存率提高。使用从mIL-5处理的小鼠（1微克/天，从第-10天至-1天）回收的PEC进行的温氏试验实验表明，这些PEC可介导针对Meth-A肉瘤细胞的抗肿瘤活性。此外，当治愈的小鼠再次注射Meth-A肉瘤细胞或同基因的MOPC104E细胞时，它们可排斥Meth-A肉瘤细胞，但不能排斥MOPC104E细胞，这表明已产生免疫记忆。这些结果表明IL-5增强了PEC的杀肿瘤活性，但我们没有迹象表明杀肿瘤活性是通过mIL-5依赖性机制介导的。
