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血清和支气管肺泡灌洗液中炎症细胞因子水平与青年支气管扩张症患者基因多态性的关系。

Relation between inflammatory cytokine levels in serum and bronchoalveolar lavage fluid and gene polymorphism in young adult patients with bronchiectasis.

机构信息

1 Department of Chest Diseases, 2 Department of Pathology, GATA Haydarpasa Training Hospital, Istanbul, Turkey.

出版信息

J Thorac Dis. 2014 Jun;6(6):684-93. doi: 10.3978/j.issn.2072-1439.2014.04.14.

Abstract

AIM

Bronchiectasis develops as a result of genetic and environmental factors and its etiopathogenesis is not still clear. Recent studies have revealed that inflammatory cytokines, which are formed as a result of chronic infection and inflammation, play a role in the pathogenesis of bronchiectasis. For this purpose, the level of inflammatory cytokines in bronchiectasis and the presence or absence of a genetic predisposition with the gene polymorphism of these cytokines was investigated.

MATERIAL AND METHODS

A total of 60 patients, 40 study cases and 20 controls, which were monitored with the diagnosis of bronchiectasis were included in the study. In these individuals, cytokine levels [interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α] in serum and bronchoalveolar lavage (BAL) fluid, along with the routine blood tests, were determined. Furthermore, the polymorphism in IL-6, IL-8, IL-10, and TNF-α cytokine genes and its frequency were studied in the obtained DNA by the automatic sequence analysis method and the results were compared.

FINDINGS

It was found that in serum and BAL fluid of the patient group, the IL-8 level was high, whereas the IL-10 level was low (P<0.05). No significant difference was detected in the other cytokines (P>0.05). It was found that in cytokine gene polymorphisms IL-8 -251 A/T, IL-10 -592 A/C, and IL-10 -819 T/C genotypes are associated with increased risk of bronchiectasis. It was detected that the IL-8 -251 A/T genotype increased the risk of having the disease by 4.19 fold. (OR =4.19, 95% CI =1.24-14.17, P=0.021). The IL-10 -592 C/A genotype increased the risk of having the disease by 5.71 fold (OR = 5.71, 95% CI =1.35-24.06, P=0.017) and the IL-10 -819 T/C genotype increased the risk of having the disease by 5.06 fold (OR =5.06, 95% CI =1.20-21.27, P=0.048). No significant correlation was found between the other polymorphisms and bronchiectasis.

CONCLUSIONS

The IL-8, IL-10 levels and the gene polymorphism of these cytokines differ. In addition to detecting higher levels of pro-inflammatory IL-8 and lower levels of anti-inflammatory IL-10, detection of gene polymorphism related to these two cytokines in bronchiectasis gives rise to the thought that cytokines may have role in a predisposition to bronchiectasis. However, as the number of patients is small, precise remarks could not be made on this subject. There is need for further studies include a larger number of patients.

摘要

目的

支气管扩张症是由遗传和环境因素共同导致的,其发病机制尚不清楚。最近的研究表明,慢性感染和炎症导致的炎症细胞因子在支气管扩张症的发病机制中起作用。为此,本研究旨在探讨支气管扩张症患者血清和支气管肺泡灌洗液(BAL)中炎症细胞因子的水平以及这些细胞因子的基因多态性与遗传易感性的关系。

材料和方法

共纳入 60 例患者,40 例研究病例和 20 例对照。在这些个体中,测定了血清和 BAL 液中的细胞因子水平[白细胞介素(IL)-6、IL-8、IL-10 和肿瘤坏死因子(TNF)-α],并进行了常规血液检查。此外,通过自动序列分析方法研究了获得的 DNA 中 IL-6、IL-8、IL-10 和 TNF-α细胞因子基因的多态性及其频率,并进行了比较。

结果

发现患者组血清和 BAL 液中 IL-8 水平升高,而 IL-10 水平降低(P<0.05)。其他细胞因子无显著差异(P>0.05)。细胞因子基因多态性研究发现,IL-8-251 A/T、IL-10-592 A/C 和 IL-10-819 T/C 基因型与支气管扩张症的发病风险增加相关。IL-8-251 A/T 基因型使疾病的发病风险增加了 4.19 倍(OR=4.19,95%CI=1.24-14.17,P=0.021)。IL-10-592 C/A 基因型使疾病的发病风险增加了 5.71 倍(OR=5.71,95%CI=1.35-24.06,P=0.017),IL-10-819 T/C 基因型使疾病的发病风险增加了 5.06 倍(OR=5.06,95%CI=1.20-21.27,P=0.048)。其他多态性与支气管扩张症无显著相关性。

结论

IL-8、IL-10 水平及其细胞因子的基因多态性不同。除了检测到促炎细胞因子 IL-8 水平升高和抗炎细胞因子 IL-10 水平降低外,支气管扩张症患者中与这两种细胞因子相关的基因多态性的检测提示细胞因子可能在支气管扩张症的易感性中起作用。然而,由于患者数量较少,因此无法对此主题进行精确的说明。需要进一步的研究,包括更多的患者。

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