The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism

The effect of age and gender on cytokine production by human peripheral blood mononuclear cells and markers of bone metabolism
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DOI:
10.1016/s0531-5565(03)00189-x
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发表时间:
2003-10-01
影响因子:
3.9
通讯作者:
Tragl, KH
Tragl, KH
中科院分区:
医学2区
文献类型:
--
作者:
Pietschmann, P;Gollob, E;Tragl, KH

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背景衰老与免疫功能、肌肉骨骼系统和性激素水平下降的各种改变有关。雌激素在调节骨转换中起重要作用,还调节细胞因子如白细胞介素-1和-6和肿瘤坏死因子-α的产生。因此,我们研究了年龄和性别对单核细胞产生细胞因子和骨代谢标志物的影响。从年轻和老年受试者中分离外周血单核细胞;通过四色流式细胞术进行用离子霉素和PMA(T细胞)或LPS(单核细胞)刺激后细胞因子产生的细胞内检测。用放射免疫法和酶联免疫吸附法测定性激素水平和骨代谢指标。当我们比较老年女性和年轻女性时,我们发现γ干扰素、白细胞介素-2、-4、-10和-13阳性的T细胞比例增加。此外,在CD 8(+)人群中产生白细胞介素-4或干扰素-γ的细胞百分比在老年妇女组中更高。相比之下,老年女性中肿瘤坏死因子-a或白细胞介素-6阳性的单核细胞比例低于年轻女性。在老年男性中,更高百分比的T细胞产生白细胞介素-2,-4和-13。在老年男性组中,我们发现在CD 4(+)或CD 8(+)人群中产生白细胞介素-4的细胞频率较高。此外,在老年人的单核细胞中,我们发现白细胞介素-1 β和肿瘤坏死因子-α阳性细胞的百分比增加。骨代谢标志物的数据表明老年人骨转换增加。我们的数据表明,衰老与骨代谢和T细胞和单核细胞产生的细胞因子的显着改变。对于特定的细胞因子(T细胞中的干扰素-γ和白介素-10,单核细胞中的白介素-6和肿瘤坏死因子-α),这些变化具有性别特异性。(C)2003年爱思唯尔公司All rights reserved.
Background. Aging has been associated with various alterations of immune functions, the musculoskeletal system and a decline of sex hormone levels. Estradiol has a central role in the regulation of bone turnover and also modulates the production of cytokines such as interleukin-1 and -6 and tumor necrosis factor-alpha. We therefore studied the effect of age and gender on cytokine production by mononuclear cells and markers of bone metabolism.Methods. Peripheral blood mononuclear cells were isolated from young and elderly subjects; intracellular detection of cytokine production after stimulation with ionomycine and PMA (T cells) or LPS (monocytes) was performed by four color flow cytometry. Sex hormone levels and markers of bone metabolism were measured by RIA or ELISA.Results. When we compared elderly to young women we found an increased proportion of T cells that were positive for interferon-gamma, interleukin-2, -4, -10 and -13. Also the percentage of cells producing interleukin-4 or interferon-gamma within the CD8(+) population was higher in the group of elderly women. In contrast, proportionally fewer monocytes of elderly women were positive for tumor necrosis factor-a or interleukin-6 than those of young women. In elderly men a higher percentage of T cells produced interleukin-2, -4 and -13. In the group of aged men we found a higher frequency of cells that produced interleukin-4 within the CD4(+) or CD8(+) population. Moreover, within monocytes of elderly men we found an increased percentage of cells positive for both interleukin-1beta and tumor necrosis factor-alpha. The data on markers of bone metabolism indicated an increase of bone turnover in old age.Conclusion. Our data demonstrate that aging is associated with significant alterations of bone metabolism and cytokine production by T cells and monocytes. For particular cytokines (interferon-gamma and interleukin-10 in T cells, interleukin-6 and tumor necrosis factor-a in monocytes) these changes are gender specific. (C) 2003 Elsevier Inc. All rights reserved.