Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence
Proinflammatory profile of in vitro monocytes in the ageing is affected by lymphocytes presence
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DOI：
10.1186/1742-4933-10-22
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发表时间：
2013-06-08
影响因子：
7.9
通讯作者：
Lara, Vanessa Soares
中科院分区：
文献类型：
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作者：
Pinke, Karen Henriette;Calzavara, Bruno;Lara, Vanessa Soares
背景：衰老与免疫功能的复杂和持续重塑有关，导致对感染和其他疾病的易感性增加。疗养院和医院中存在的革兰氏阴性微生物引起的感染是老年人中最常见的感染之一，主要由先天免疫细胞对抗。尽管先天免疫的功能似乎在衰老过程中比适应性免疫机制得到了更多的保留，但这两个系统在体内以一种整合的方式运作，因此免疫系统一部分的损伤不可避免地影响到另一部分，因为它们是防御网络的一部分。本研究的目的是研究来自健康青年和老年受试者的单核细胞在体外产生促炎（tnf - α, IL-6, IL-1 β， CXCL-8和MCP-1）和抗炎（tgf - β和IL-10）细胞因子，是否受到脂多糖刺激（基础）。通过PBMCs，我们还研究了在相同的实验条件下，在淋巴细胞存在的情况下，这些不同患者组的细胞因子谱是否发生了改变。结果：老年单核细胞tnf - α、MCP-1的基础生成量高于年轻单核细胞，tgf - β的基础生成量低于年轻单核细胞。无论年龄或刺激是否存在，PBMC都显示出相似的细胞因子产生。在淋巴细胞存在的情况下，无论年龄大小，自发产生的IL-10较高，tgf - β较单核细胞低。与年轻患者单核细胞纯培养相比，lps刺激后淋巴细胞的存在导致IL-6、IL-1 β、MCP-1和IL-10升高，CXCL-8和tgf - β降低。随着年龄的增长，除了CXCL-8和tgf - β的产生在单核细胞和LPS刺激的PBMC之间相同外，观察到同样的差异。结论：这些发现强化了在老年人中经常报道的全身炎症老化状态，并被认为是许多疾病的易感性因素。尽管如此，仅来自老年人单核细胞的细胞因子产生显示出改变，而淋巴细胞则没有，这表明淋巴细胞对单核细胞具有免疫调节作用。此外，lps刺激的PBMC在年轻和老年志愿者之间产生模式的差异可能与一生中对革兰氏阴性菌的反应不平衡有关。
Background: Aging is associated with complex and constant remodeling of the immune function, resulting in an increasing susceptibility to infection and others diseases. The infections caused by Gram-negative microorganisms, present in nursing homes and hospitals, constitute one of the most common infections in the elderly, and are mainly combated by innate immune cells. Although the functions of innate immunity seem more preserved during aging than of adaptive immune mechanisms, two systems operate in an integrated way in the body, so that injury in one part of the immune system inevitably affects the other as they are part of a defensive network. The aim of this study was to investigate the in vitro production of proinflammatory (TNF-alpha, IL-6, IL-1 beta, CXCL-8 and MCP-1) and anti-inflammatory (TGF-beta and IL-10) cytokines by monocytes, stimulated or not (basal) with lipopolysaccharide, from healthy young and elderly subjects. By means of PBMCs, we also studied if cytokine profile is altered in these different patient groups, in the presence of lymphocytes, under the same experimental conditions.Results: The monocytes from elderly presented higher basal production of TNF-alpha, MCP-1 and lower of TGF-beta than young monocytes. PBMC showed similar cytokines production, irrespective age or stimulation presence. In the presence of lymphocytes, the spontaneous production of IL-10 was higher and of TGF-beta was lower than monocytes, regardless of age. After LPS-stimulation, the presence of lymphocytes resulted in increased IL-6, IL-1 beta, MCP-1 and IL-10 and decreased CXCL-8 and TGF-beta in comparison to pure culture of monocytes from young patients. With age, the same differences were observed, except for CXCL-8 and TGF-beta which production was the same between monocytes and PBMC stimulated with LPS.Conclusion: These findings reinforce the systemic state of inflamm-aging frequently reported in elderly and considered a factor of susceptibility to numerous diseases. Still, the cytokine production from just monocytes of the elderly showed alterations, while in the lymphocyte presence not, suggesting an immunomodulator role of lymphocytes on monocytes. In addition, the differences between the production patterns by LPS-stimulated PBMC between young and elderly volunteers can be related with an imbalance in response against Gram-negative bacteria in throughout life.