系统性硬化症患者中α-防御素水平升高与间质性肺炎的关联。
Association of elevated α-defensin levels with interstitial pneumonia in patients with systemic sclerosis.
作者信息
Sakamoto Noriho, Kakugawa Tomoyuki, Hara Atsuko, Nakashima Shota, Yura Hirokazu, Harada Tatsuhiko, Ishimoto Hiroshi, Yatera Kazuhiro, Kuwatsuka Yutaka, Hara Toshihide, Ichinose Kunihiro, Obase Yasushi, Ishimatsu Yuji, Kohno Shigeru, Mukae Hiroshi
机构信息
Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Department of Respiratory Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
出版信息
Respir Res. 2015 Dec 10;16:148. doi: 10.1186/s12931-015-0308-1.
BACKGROUND
Interstitial lung disease (ILD) is the leading cause of mortality in patients with systemic sclerosis (SSc). Although the pathogenesis of SSc-ILD is not well understood, neutrophils may play a pivotal role in this process. Neutrophils store azurophil granules that contain defensins, antimicrobial peptides that function in regulating the inflammatory response, and IL-8, a potent chemoattractant for neutrophils. The present study evaluated the levels of defensins and IL-8 in patients with SSc-ILD to determine their roles in disease pathogenesis.
METHODS
Defensins (also known as human neutrophil peptides, HNPs) and IL-8 levels were measured in the serum and bronchoalveolar lavage fluid (BALF) of 33 patients with SSc-ILD and in 20 healthy controls by using ELISA.
RESULTS
BALF analysis revealed a significant increase in HNPs in SSc-ILD patients (median; 240.0 pg/mL) than that of healthy controls (79.7 pg/mL). Additionally, IL-8 levels were higher in SSc-ILD patient serum and BALF as compared to healthy controls (16.4 pg/mL vs. 5.8 pg/mL and 15.4 pg/mL vs. 14.5 pg/mL, respectively). However, plasma HNPs levels were relatively unchanged. HNP and IL-8 levels in patient BALF displayed a significant positive correlation significantly correlated (r = 0.774, p <0.01), and which also correlated with clinical disease parameters--such as ILD biomarkers, pulmonary function tests, ratio of neutrophils and eosinophils in BALF, tricuspid regurgitation peak gradient (TRPG), and the extent of high-resolution computed tomography (HRCT) findings in the lung. Levels of plasma HNPs and serum IL-8 did not show a significant correlation with any clinical parameter. SSc-ILD progression was evaluated by pulmonary function tests, but no association was observed between VC change ratios and HNPs or IL-8 levels.
CONCLUSIONS
BALF levels of HNPs and IL-8 were higher in SSc-ILD than in healthy controls, and are associated with various clinical disease parameters. Further studies are needed to clarify the role of defensins and IL-8 in SSc-ILD pathogenesis.
背景
间质性肺病（ILD）是系统性硬化症（SSc）患者的主要死亡原因。尽管SSc-ILD的发病机制尚未完全明确，但中性粒细胞可能在此过程中起关键作用。中性粒细胞储存嗜天青颗粒，其中含有防御素（一种在调节炎症反应中起作用的抗菌肽）和白细胞介素-8（IL-8，一种对中性粒细胞有强效趋化作用的物质）。本研究评估了SSc-ILD患者体内防御素和IL-8的水平，以确定它们在疾病发病机制中的作用。
方法
采用酶联免疫吸附测定法（ELISA），检测了33例SSc-ILD患者及20名健康对照者血清和支气管肺泡灌洗液（BALF）中的防御素（也称为人中性粒细胞肽，HNPs）和IL-8水平。
结果
BALF分析显示，SSc-ILD患者的HNPs水平（中位数为240.0 pg/mL）显著高于健康对照者（79.7 pg/mL）。此外，与健康对照者相比，SSc-ILD患者血清和BALF中的IL-8水平更高（分别为16.4 pg/mL对5.8 pg/mL和15.4 pg/mL对14.5 pg/mL）。然而，血浆中HNPs水平相对未变。患者BALF中的HNP和IL-8水平呈显著正相关（r = 0.774，p <0.01），且与临床疾病参数相关，如ILD生物标志物、肺功能测试、BALF中中性粒细胞与嗜酸性粒细胞的比例、三尖瓣反流峰值梯度（TRPG）以及肺部高分辨率计算机断层扫描（HRCT）结果的范围。血浆HNPs水平和血清IL-8水平与任何临床参数均无显著相关性。通过肺功能测试评估SSc-ILD的进展情况，但未观察到肺活量（VC）变化率与HNPs或IL-8水平之间存在关联。
结论
SSc-ILD患者BALF中的HNPs和IL-8水平高于健康对照者，且与多种临床疾病参数相关。需要进一步研究以阐明防御素和IL-8在SSc-ILD发病机制中的作用。
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