Sex and parity modulate cytokine production during murine ageing

Sex and parity modulate cytokine production during murine ageing
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DOI:
10.1046/j.1365-2249.1997.4851387.x
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发表时间:
1997-09-01
影响因子:
4.6
通讯作者:
Pilet, C
Pilet, C
中科院分区:
医学3区
文献类型:
--
作者:
Barrat, F;Lesourd, B;Pilet, C

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我们之前已经证明,在小鼠衰老过程中,与怀孕或性别相关的生理激素差异会影响与年龄相关的单核细胞群体的分布。为了确定这种变化是否与年龄相关的T细胞功能改变有关,我们检测了C57B1/6小鼠脾细胞在刀豆蛋白A激活后的体外分泌的主要T细胞免疫调节细胞因子(IL-2、IL-4、干扰素-γ、IL-3、IL-6和粒细胞-巨噬细胞集落刺激因子)的分泌。这项研究包括2个月、8个月、15个月和23个月大的经产和处女雌性和雄性。产次(8月)的短期效应表现为经产母鼠(8月龄)的干扰素-γ水平下降和IL-2水平保持不变,而处女鼠的干扰素-γ水平不变,IL-2水平下降。经产妇(15个月)比处女(23个月)的IL-4产生增加出现得更早。经产妇在8个月和15个月时IL-4/干扰素-γ和IL-4/IL-2的比值分别升高,表明怀孕改变了Th1/Th2的平衡。在成年后期(15个月),经产女性的IL-6和GM-CSF产量高于处女男性或女性。性别差异也被注意到:随着年龄的增长,男性的干扰素-γ的分泌量低于女性。这项研究强调,与年龄相关的细胞因子产生的变化的开始、幅度和动力学是与性别和性别相关的。这些变化可能会影响与年龄相关的疾病的发生率,并可能解释女性更长寿的原因。
We have previously shown that physiological hormone differences related to pregnancy or sex affect the age-related distribution of mononuclear cell populations during murine ageing. To determine whether such changes are involved in the age-related changes in functions of T cells, we examined the secretion of major T cell immunoregulatory cytokines (IL-2, IL-4, interferon-gamma (IFN-gamma), IL-3, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) of in vitro concanavalin A-activated spleen cells of C57B1/6 mice. The study included multiparous and virgin females and males at 2, 8, 15 and 23 months of age. Short-term effects of parity (8 months) were evidenced by the decrease of IFN-gamma and the preserved IL-2 production in multiparous females (8 months), while IFN-gamma was unchanged and IL-2 decreased in virgin mice. The increase in IL-4 production appeared earlier in multiparous females (15 months) than in virgin mice (23 months). The increase in IL-4/IFN-gamma and IL-4/IL-2 ratios at 8 and 15 months, respectively, in multiparous females, suggests that pregnancy modifies the Th1/Th2 equilibrium. In late adulthood (15 months), IL-6 and GM-CSF production was higher in multiparous females than in virgin males or females. Sex differences were also noticed: IFN-gamma secretion capacity was lower in males than in females during ageing. This study underlines that the onset, magnitude and kinetics of the age-related changes in cytokine production are parity-and sex-dependent. These changes probably influence the incidence of age-related diseases and may explain the greater longevity of females.