Sämpi Maritta, Ukkola Olavi, Päivänsalo Markku, Kesäniemi Y Antero, Binder Christoph J, Hörkkö Sohvi
Department of Internal Medicine, Biocenter Oulu, Oulu, Finland.
J Am Coll Cardiol. 2008 Oct 21;52(17):1370-8. doi: 10.1016/j.jacc.2008.06.047.
This study's aim was to assess the role of interleukin (IL)-5 in modulating the levels of antibodies binding to oxidized low-density lipoprotein (OxLDL) in human atherosclerosis.
Various pro- and anti-inflammatory cytokines have been implicated in atherogenesis, and recent findings in mice indicate that the cytokine IL-5 plays a protective role in atherosclerosis in part via the induction of antibodies binding to OxLDL.
Plasma IL-5 levels and antibody titers to 2 most commonly used models of OxLDL (copper OxLDL and malondialdehyde-modified LDL) were measured in 1,011 Finnish middle-aged subjects with chemiluminescent enzyme-linked immunosorbent assay. Intima-media thickness (IMT) was assessed ultrasonographically from the internal carotid artery, the bifurcation, and the common carotid artery.
There was a significant positive association between plasma IL-5 levels and antibody titers to copper OxLDL (p = 0.010 and p = 0.044, immunoglobin [Ig] M and G, respectively) and IgM to malondialdehyde-modified LDL (p < 0.001) in the association analysis performed between different IL-5 quartiles. Furthermore, plasma IL-5 levels were found to be inversely associated with bifurcational IMT, and even after adjustments for traditional risk factors of atherosclerosis (age, gender, smoking, systolic blood pressure, LDL, and body mass index), IL-5 remained an independent determinant of the mean bifurcational IMT (p = 0.010).
Our data demonstrate that plasma IL-5 levels are related to the plasma levels of antibodies binding to OxLDL and to decreased subclinical atherosclerosis in humans. These results are in line with earlier findings in murine atherosclerosis and indicate for the first time that IL-5 may play a role in human atherosclerosis.
本研究旨在评估白细胞介素(IL)-5在调节人类动脉粥样硬化中与氧化低密度脂蛋白(OxLDL)结合的抗体水平方面的作用。
多种促炎和抗炎细胞因子与动脉粥样硬化的发生有关,最近在小鼠中的研究结果表明,细胞因子IL-5部分通过诱导与OxLDL结合的抗体在动脉粥样硬化中发挥保护作用。
采用化学发光酶联免疫吸附测定法,对1011名芬兰中年受试者的血浆IL-5水平以及针对2种最常用的OxLDL模型(铜OxLDL和丙二醛修饰的LDL)的抗体滴度进行了测量。通过超声检查评估颈内动脉、分叉处和颈总动脉的内膜中层厚度(IMT)。
在不同IL-5四分位数之间进行的关联分析中,血浆IL-5水平与针对铜OxLDL的抗体滴度(分别为免疫球蛋白[Ig]M和G,p = 0.010和p = 0.044)以及针对丙二醛修饰的LDL的IgM(p < 0.001)之间存在显著正相关。此外,发现血浆IL-5水平与分叉处IMT呈负相关,即使在对动脉粥样硬化的传统危险因素(年龄、性别、吸烟、收缩压、LDL和体重指数)进行调整后,IL-5仍然是平均分叉处IMT的独立决定因素(p = 0.010)。
我们的数据表明,血浆IL-5水平与人类中与OxLDL结合的抗体的血浆水平以及亚临床动脉粥样硬化的减轻有关。这些结果与小鼠动脉粥样硬化的早期研究结果一致,并首次表明IL-5可能在人类动脉粥样硬化中起作用。