Gorczynski R M, Bessler W G, Chung S, Cinader B, Hoffmann P, Modolell M, Ramakrishna V, Reischel E T, Waelli T, Westphal O
Department of Surgery, University of Toronto, Ontario, Canada.
Immunol Lett. 1998 Feb;60(2-3):157-64. doi: 10.1016/s0165-2478(97)00149-1.
BALB/c, DBA/2 and C57BL/6 mice of different ages (ranging from 8 to 110 weeks of age) were used as spleen cell donors to assay cytokine production from ConA activated spleen and Peyer's Patch (PP) lymphocytes. As reported in an earlier publication, there was an age-related decline in IL-2 production in all strains, with a general increase in IL-4 and IL-10 production with age, this being particularly marked for PP cell preparations. Similar conclusions were reached from independent analysis of CD44hi and CD44lo cell populations in these groups (memory vs. naive cells, respectively). Interestingly, IL-6 production was dramatically increased (some 4-5-fold in the different strains) and significantly increased levels of IL-6 were detected in the serum of aged mice. A previously described sheep fetal liver extract was able to reverse, to varying degrees, these cytokine changes associated with aging. Interestingly, when cells from aged mice were adoptively transferred to lethally irradiated young (8 week) recipients, the cytokine production phenotype of cells harvested from recipient mice 3 weeks later was that of the aged donor, unless recipients were treated continually with extract. Treatment of the donor alone produced minimal changes in cytokine production 3 weeks following adoptive transfer. The effect of extract was reversed in treated aged mice by concomitant daily intravenous infusion of the competitive inhibitor of nitric oxide synthesis (NG-monomethyl-L-arginine (NMMA)), which also decreased the increased serum nitrate levels in mice treated with extract. Our data suggest an important role for reactive nitrogen products, themselves induced by fetal liver extract, in age-associated changes in cytokine production.
不同年龄（8至110周龄）的BALB/c、DBA/2和C57BL/6小鼠被用作脾细胞供体，以检测伴刀豆球蛋白A激活的脾脏和派伊尔结（PP）淋巴细胞产生细胞因子的情况。如早期一篇出版物中所报道，所有品系中白细胞介素-2（IL-2）的产生均随年龄下降，IL-4和IL-10的产生随年龄总体增加，这在PP细胞制剂中尤为明显。对这些组中的CD44高表达和CD44低表达细胞群体（分别为记忆细胞与幼稚细胞）进行独立分析也得出了类似结论。有趣的是，IL-6的产生显著增加（不同品系中约增加4至5倍），并且在老年小鼠血清中检测到IL-6水平显著升高。一种先前描述的羊胎肝提取物能够不同程度地逆转这些与衰老相关的细胞因子变化。有趣的是，当将老年小鼠的细胞过继转移至经致死性照射的年轻（8周龄）受体时，3周后从受体小鼠收获的细胞的细胞因子产生表型为老年供体的表型，除非受体持续用提取物处理。仅对供体进行处理在过继转移3周后细胞因子产生的变化极小。通过每日静脉内输注一氧化氮合成竞争性抑制剂（NG-单甲基-L-精氨酸（NMMA）），提取物对老年小鼠的作用在处理后被逆转，这也降低了用提取物处理的小鼠血清中升高的硝酸盐水平。我们的数据表明，由胎肝提取物自身诱导产生的活性氮产物在与年龄相关的细胞因子产生变化中起重要作用。
