Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice
Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice
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DOI：
10.1007/s11357-010-9151-y
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发表时间：
2010-12-01
期刊：
影响因子：
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通讯作者：
De la Fuente, Monica
中科院分区：
文献类型：
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作者：
Arranz, Lorena;Lord, Janet M.;De la Fuente, Monica
据报道，小鼠的免疫细胞功能得以保留，从而获得了极长的寿命。由于细胞因子是免疫反应的主要调节剂，我们的目的是确定中年人（44 +/- 4 周）、老年（69 +/- 4 周）、非常老（92 +/- 4 周）和极长寿者（125 +/- 4 周）的腹膜白细胞在基础和有丝分裂原（ConA 和 LPS）刺激条件下培养的离体分泌的 21 种细胞因子的水平。周）ICR（CD1）雌性小鼠。通过多重发光测定法测量细胞因子的分泌。在老年和非常老的动物中，促炎性 IL-1β、IL-6、IL-12 (p70)、IFN-γ 和 TNF-α 的基础水平升高，同时 IL-10 降低。相比之下，极长寿小鼠维持了中年小鼠的整体细胞因子谱，尽管 IL-2、IL-9、IL-10、IL-13 和 IL-12 (p40) 的基础分泌有所增加。在 LPS 和/或 ConA 刺激的条件下，来自年老和非常年老动物的白细胞在分泌 Th1 细胞因子 IL-3、IL-12p70、IFN-gamma 和 TNF-α 方面表现出明显受损的反应； Th2 细胞因子 IL-6、IL-4、IL-10 和 IL-13；以及调节细胞因子 IL-2、IL-5 和 IL-17。极长寿小鼠保留了类似中年的细胞因子谱，其中最显着的效果是 IL-2 对 ConA 的反应，在老年和非常老的小鼠中反应最小，但相对于极长寿小鼠的中年水平有所增加。尽管在长寿和中年小鼠中发现 LPS 诱导的 KC 和 MCP-1 以及刀豆蛋白 A 诱导的 MCP-1、MIP-1 β 和 RANTES 的分泌相似，但 KC、MCP-1、MIP-1 β 和 RANTES 的趋化因子反应变化较大。因此，极端长寿的动物仅表现出最小的炎症特征，远低于老年和非常老年组，也低于中年动物，这可能是由抗炎细胞因子（如 IL-10）的增加介导的。这与适当的 Th1/Th2 和调节性细胞因子分泌对免疫刺激的强烈反应有关，这似乎是长寿动物中报告的保留免疫反应的一个因素，从而延长了它们的寿命。
Preserved immune cell function has been reported in mice that achieve extreme longevity. Since cytokines are major modulators of immune responses, we aimed to determine the levels of 21 cytokines secreted ex vivo by peritoneal leukocytes cultured under basal- and mitogen- (conconavalin A (ConA) and LPS) stimulated conditions in middle-aged (44 +/- 4 weeks), old (69 +/- 4 weeks), very old (92 +/- 4 weeks), and extreme long-lived (125 +/- 4 weeks) ICR (CD1) female mice. The secretion of cytokines was measured by multiplex luminometry. Increased basal levels of proinflammatory IL-1 beta, IL-6, IL-12 (p70), IFN-gamma, and TNF-alpha were seen in the old and very old animals, accompanied by decreased IL-10. In contrast, the extreme long-lived mice maintained the overall cytokine profile of middle-aged mice, though the basal secretion of IL-2, IL-9, IL-10, IL-13, and IL-12 (p40) was raised. Under LPS- and/or ConA-stimulated conditions, leukocytes from old and very old animals showed a significantly impaired response with respect to secretion of Th1 cytokines IL-3, IL-12p70, IFN-gamma, and TNF-alpha; Th2 cytokines IL-6, IL-4, IL-10, and IL-13; and the regulatory cytokines IL-2, IL-5, and IL-17. Extreme long-lived mice preserved the middle-aged-like cytokine profile, with the most striking effect seen for the IL-2 response to ConA, which was minimal in the old and very old mice but increased with respect to the middle-aged level in extreme long-lived mice. Chemokine responses in regard to KC, MCP-1, MIP1 beta, and RANTES were more variable, though similar secretion of LPS-induced KC and MCP-1 and ConA-induced MCP-1, MIP-1 beta, and RANTES was found in long-lived and middle-aged mice. Thus, extreme long-lived animals showed only a minimal inflammatory profile, much lower than the old and very old groups and also lower than the middle-aged, which is likely mediated by the increase of anti-inflammatory cytokines such as IL-10. This was coupled to a robust response to immune stimuli across an appropriated Th1/Th2 and regulatory cytokine secretion, which seems to be a factor contributing to the preserved immune response reported in very long-lived animals and thus to their extended longevity.