Pongratz Georg, Lowin Torsten, Kob Robert, Buettner Roland, Bertsch Thomas, Bollheimer L Cornelius
Department of Rheumatology, Hiller Research Center Rheumatology, University of Duesseldorf, Moorenstr. 5, 40225 Duesseldorf, Germany.
Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
Immun Ageing. 2015 Sep 28;12:12. doi: 10.1186/s12979-015-0040-1. eCollection 2015.
The immune system undergoes several alterations of innate and adaptive immunity during ageing. The main features of the aged immune system are a reduced diversity of T cell receptors and a reduced activity of innate immune cells with subsequent changes in adaptive immunity resulting in a less effective, less specific, and dys-regulated immune response and in an increased susceptibility towards infection, malignancy, and autoimmunity. The process is referred to as immunosenescence and is also modulated by environmental modifiers, such as dietary factors. High fat diet (HFD), via direct modulation of immune cell function by fatty acids and/or increased body fat mass, influences immune function. However, it is not clear whether HFD is beneficial or detrimental for the functioning of the ageing immune system.
Male Wistar rats fed with either a high fat diet (HFD 43 en% of fat) or control diet (SD, 25 en% of fat) over up to 24 month and were analyzed for plasma IL-1β, IL-6, TNF, IgM, IgG1, IgA, IgG2a, IgG2b, IgG2c, light chains lambda and kappa, testosterone, prolactin and percentage of splenic B cells and apoptosis rate, respectively.
In general, all analyzed immunoglobuline isotypes increased with age, except for IgA. This increase was attenuated by HFD. In HFD and SD rats the percentage of B cells in the spleen and also their apoptotic rate was lower in aged as compared to young animals with no additional diet-induced effect. Testosterone and prolactin levels were lower in old animals, as expected. There was a statistical trend towards an increased prolactin/testosterone ratio in middle aged (6-12 monthsnth) HFD rats as compared to SD. IL-6 was neither affected by HFD nor age. On the other hand, HFD rats showed a decrease in IL-1β as compared to SD, which correlated with the above-mentioned suppressive effect on immunoglobulin isotypes, especially IgM.
In Wistar rats, HFD reveals an immunosuppressive effect in ageing animals by decreasing immunoglobulins, especially IgM, and IL-1β when compared to SD.
免疫系统在衰老过程中会经历先天性和适应性免疫的多种改变。衰老免疫系统的主要特征是T细胞受体多样性降低以及先天性免疫细胞活性降低，随后适应性免疫发生变化，导致免疫反应效率降低、特异性降低且调节失调，并增加对感染、恶性肿瘤和自身免疫的易感性。这个过程被称为免疫衰老，它也受到环境调节因素的影响，如饮食因素。高脂饮食（HFD）通过脂肪酸对免疫细胞功能的直接调节和/或增加体脂量来影响免疫功能。然而，尚不清楚高脂饮食对衰老免疫系统的功能是有益还是有害。
雄性Wistar大鼠分别喂食高脂饮食（脂肪含量43%能量）或对照饮食（标准饮食，脂肪含量25%能量）长达24个月，并分别分析血浆白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF）、免疫球蛋白M（IgM）、免疫球蛋白G1（IgG1）、免疫球蛋白A（IgA）、免疫球蛋白G2a（IgG2a）、免疫球蛋白G2b（IgG2b）、免疫球蛋白G2c（IgG2c）、λ轻链和κ轻链、睾酮、催乳素以及脾B细胞百分比和凋亡率。
总体而言，除IgA外，所有分析的免疫球蛋白亚型均随年龄增加。高脂饮食减弱了这种增加。在高脂饮食和标准饮食大鼠中，与年轻动物相比，老年动物脾脏中B细胞的百分比及其凋亡率均较低，且无额外的饮食诱导效应。正如预期的那样，老年动物的睾酮和催乳素水平较低。与标准饮食相比，中年（6 - 12个月）高脂饮食大鼠的催乳素/睾酮比值有增加的统计学趋势。IL-6既不受高脂饮食影响，也不受年龄影响。另一方面，与标准饮食相比，高脂饮食大鼠的IL-1β降低，这与上述对免疫球蛋白亚型尤其是IgM的抑制作用相关。
在Wistar大鼠中，与标准饮食相比，高脂饮食在衰老动物中表现出免疫抑制作用，可降低免疫球蛋白尤其是IgM和IL-1β的水平。
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