Cytokine profile features in women with reproductive disorders exposed to excessive environmental contamination with hydroxybenzene

O. Kazakova, O. Dolgikh
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Abstract

Excessive activity of cytokines, as well as their deficiency, promote a regulatory imbalance of immune system, which may cause persistent inflammation and, as a consequence, loss of pregnancy. The purpose of our work was to study the role of cytokine expression in the development of endometriosis in women exposed to excessive environmental contamination with hydroxybenzene. The study involved 106 women of reproductive age, divided into 4 groups according to two criteria: the presence or absence of reproductive disorders (endometriosis), as well as levels of blood contamination with hydroxybenzene compared to the reference ranges. The groups of women were comparable in age, ethnicity, and social status. The level of phenol in blood was measured by gas chromatography, and the cytokine levels were determined by enzyme immunoassay. The use of parametric and nonparametric statistical criteria as well as adjustments for multiple Bonferoni comparisons, allowed us to establish significant differences between the groups, according to the levels of IL-1β, IL-8, IL-10. The expression of interleukin 8 (IL-8) in women with endometriosis was found to be significantly higher than in healthy ones. At the same time, the observed features of IL-8, interleukin 1β (IL-1β) expression correlate with the overproduction of interleukin 10 (IL-10) associated with excessive contamination of bio-environments with hydroxybenzene. The results of using non-parametric correlation analysis of the Spearman data revealed a positive correlation between IL-10 production and hydroxybenzene levels in the blood, as well as inverse relationship between IL-10 and IL-8 expression. Thus, evidence has been obtained of the involvement of exogenous estrogen hydroxybenzene in development of reproductive disorders, probably, formed under active participation of increased anti-inflammatory IL-10 cytokine, which, by antagonism to proinflammatory mediators (e.g., IL-8), seems to promote apparent transition from acute phase of endometriosis to chronic disorder, thus reducing the reproductive potential of women. It is known that IL-8 expression significantly correlates with development of endometriosis, but excessive phenol exposure may increase the anti-inflammatory IL-10 expression, thereby suppressing the activity of IL-8. Suppressed activity of proinflammatory cytokines by phenol may lead to chronic inflammation and impaired reproductive functions.
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暴露于过量环境污染的羟基苯的生殖障碍妇女的细胞因子特征
细胞因子的过度活性及其缺乏会促进免疫系统的调节失衡,这可能会导致持续的炎症,从而导致流产。我们工作的目的是研究细胞因子表达在暴露于羟基苯过度环境污染的妇女子宫内膜异位症发展中的作用。这项研究涉及106名育龄妇女,根据两个标准分为4组:是否存在生殖障碍(子宫内膜异位症),以及与参考范围相比血液中羟基苯的污染水平。这些妇女群体在年龄、种族和社会地位方面具有可比性。通过气相色谱法测定血液中的苯酚水平,并通过酶免疫测定法测定细胞因子水平。使用参数和非参数统计标准以及对多种Bonferoni比较的调整,使我们能够根据IL-1β、IL-8和IL-10的水平确定各组之间的显著差异。子宫内膜异位症妇女白细胞介素8(IL-8)的表达显著高于健康妇女。同时,观察到的IL-8、白细胞介素1β(IL-1β)表达的特征与白细胞介蛋白10(IL-10)的过度产生相关,白细胞介因子10与羟基苯对生物环境的过度污染有关。Spearman数据的非参数相关分析结果显示,IL-10的产生与血液中的羟基苯水平呈正相关,IL-10与IL-8的表达呈反比。因此,已经获得了外源性雌激素-羟基苯参与生殖疾病发展的证据,可能是在抗炎IL-10细胞因子增加的积极参与下形成的,通过对抗促炎介质(如IL-8),似乎促进了从子宫内膜异位症急性期到慢性疾病的明显转变,从而降低了妇女的生殖潜力。众所周知,IL-8的表达与子宫内膜异位症的发展显著相关,但过量的苯酚暴露可能会增加抗炎IL-10的表达,从而抑制IL-8的活性。苯酚抑制促炎细胞因子的活性可能导致慢性炎症和生殖功能受损。
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