Volk M J, Pugh T D, Kim M, Frith C H, Daynes R A, Ershler W B, Weindruch R
Department of Medicine, University of Wisconsin, Madison 53706.
Cancer Res. 1994 Jun 1;54(11):3054-61.
Dietary restriction (DR) started in middle age profoundly reduces the occurrence of lymphoma in C57BL/6 mice. Here, we report immunocellular and molecular changes associated with this mode of cancer prevention. Twelve-month-old male C57BL/6 mice were either fed a control diet or subjected to moderate DR (approximately 25% < control intake). DR significantly reduced lymphoma development (incidence at 25 months, 19% of 72 control mice versus 5% of 60 DR mice). Flow cytometry of splenocytes showed that DR increased the percentage of CD4+ and CD8+ cells. Lymphomatous spleens displayed varied labeling patterns and high percentages of cells in S phase. Splenocyte c-myc expression tended to increase with age in controls and was reduced by DR. Lymphopenia and markedly reduced nucleated cell yields from peripheral lymphoid tissues were induced by DR. Serum interleukin 6 levels increased with age and were quite high (> 2500 pg/ml) in several mice with lymphoma and other histopathological findings. DR attenuated this age-associated increase. Immunohistochemical studies of lymphomatous spleens showed the presence of interleukin 6 in monocytic appearing cells but not in lymphoma cells. These observations support the possibility that an age-associated interleukin 6 dysregulation is important in lymphomagenesis.
中年开始的饮食限制（DR）能显著降低C57BL/6小鼠淋巴瘤的发生率。在此，我们报告与这种癌症预防模式相关的免疫细胞和分子变化。给12个月大的雄性C57BL/6小鼠喂食对照饮食或进行适度饮食限制（约比对照摄入量低25%）。饮食限制显著降低了淋巴瘤的发生（25个月时的发病率，72只对照小鼠中有19%发病，而60只饮食限制小鼠中只有5%发病）。脾细胞的流式细胞术显示，饮食限制增加了CD4+和CD8+细胞的百分比。淋巴瘤脾脏呈现出不同的标记模式，且S期细胞百分比很高。对照小鼠中脾细胞c-myc表达随年龄增长有增加趋势，而饮食限制使其降低。饮食限制导致淋巴细胞减少，并使外周淋巴组织中有核细胞产量显著降低。血清白细胞介素6水平随年龄增长而升高，在几只患有淋巴瘤和其他组织病理学表现的小鼠中相当高（>2500 pg/ml）。饮食限制减弱了这种与年龄相关的升高。对淋巴瘤脾脏的免疫组织化学研究显示，单核样细胞中有白细胞介素6存在，但淋巴瘤细胞中没有。这些观察结果支持这样一种可能性，即与年龄相关的白细胞介素6失调在淋巴瘤发生中很重要。
