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首页> 外文期刊>International journal of immunogenetics >The -308G/A polymorphism of TNF-alpha influences immunological parameters in old subjects affected by infectious diseases.
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The -308G/A polymorphism of TNF-alpha influences immunological parameters in old subjects affected by infectious diseases.

机译：TNF-α的-308G / A多态性影响受传染病影响的老年受试者的免疫学参数。

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摘要

Abnormal increments of pro-inflammatory cytokines (IL-6 and TNF-alpha) characterize the outbreak of infectious diseases, which are the major cause of death in the elderly. A counterbalance to the inflammation is exerted by IL-10 with an inhibitory role on TNF-alpha production. As is well known, some cytokine gene polymorphisms influence the cytokine production, playing a role as susceptibility or resistance factors against immune-mediated and infectious disease. Genetic variations in the -308A/G locus for TNF-alpha seems to affect the clinical outcome of some infectious diseases. In fact, the -308A allele is associated with severe septic shock and death. On this basis, we have screened healthy old subjects, nonagenarians and old patients affected by the acute phase of chronic obstructive bronchitis and bronchopneumonia of bacteria origin for the -308G/A locus (PCR-RFLP). Subjects are grouped in A+ (AG, AA genotypes) and A- (GG genotype) and data on IL-6, TNF-alpha, IL-10, NK cell cytotoxicity, zinc andmetallothioneins (MTs) gene expression (RT-PCR) were stratified according to different TNF-alpha genotypes. The frequency of the A allele was increased in infected patients in comparison with healthy old controls. No differences existed between A+ and A- young adult, old and nonagenarian controls in tested parameters. Conversely, A+-infected patients displayed elevated IL-6, TNF-alpha and MTmRNA, low IL-10 coupled with impaired NK cell cytotoxicity and lower zinc ion than A- patients. However, the data reported are gender independent. Therefore, the -308A polymorphism at the locus of TNF-alpha may be one of the susceptibility factor for infectious diseases in old persons, particularly considering its association to the increased release of pro-inflammatory cytokines and to the reduction of zinc release and MTs synthesis involved in the control of the inflammatory response. These data strongly suggest that the genetic screening of the -308G/A polymorphism may be a valid tool for identification of subjects needing a more appropriate therapy when affected by acute and/or recurrent infectious diseases.
机译：促炎细胞因子（IL-6和TNF-α）异常增加是传染病暴发的特征，而传染病是老年人死亡的主要原因。 IL-10对炎症起到了抵消作用，对TNF-α的产生具有抑制作用。众所周知，一些细胞因子基因多态性影响细胞因子的产生，作为抵抗免疫介导的和传染性疾病的易感性或抗性因子。 TNF-α的-308A / G位点的遗传变异似乎影响某些传染病的临床结果。实际上，-308A等位基因与严重的败血性休克和死亡有关。在此基础上，我们针对-308G / A基因座（PCR-RFLP）筛选了健康的老年受试者，非agenarians和受慢性阻塞性支气管炎和细菌性支气管肺炎急性期影响的老年患者。将受试者分为A +（AG，AA基因型）和A-（GG基因型），并就IL-6，TNF-α，IL-10，NK细胞毒性，锌和金属硫蛋白（MTs）基因表达（RT-PCR）进行数据分析根据不同的TNF-α基因型分层。与健康的老年对照相比，感染患者的A等位基因频率增加。在测试参数方面，A +和A-青年成人，老年人和非生殖器对照组之间没有差异。相反，感染A +的患者与A-患者相比，IL-6，TNF-α和MTmRNA升高，IL-10降低，NK细胞毒性减弱，锌离子降低。但是，报告的数据与性别无关。因此，TNF-α基因座的-308A多态性可能是老年人传染病的易感因素之一，尤其是考虑到它与促炎性细胞因子释放增加，锌释放和MT合成减少有关参与炎症反应的控制。这些数据强烈表明，对-308G / A多态性进行基因筛查可能是一种有效的工具，可用来识别受急性和/或复发性传染病影响而需要更适当治疗的受试者。

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