Yu H W, Dong Y Y, Dang Y H
Department of Vasculocardiology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Zhonghua Yi Xue Za Zhi. 2021 Jun 1;101(20):1518-1522. doi: 10.3760/cma.j.cn112137-20200901-02522.
To investigate the changes of interleukin-35 (IL-35) level and CD14monocytes function in patients with chronic heart failure (CHF). A total of 74 patients with CHF who were hospitalized in the Department of Cardiology of the First Affiliated Hospital of Zhengzhou University between July 2018 and June 2019 as well as 29 healthy controls (HC) were continuously enrolled. 20 ml fasting anticoagulant peripheral blood was collected in the morning, and plasma was separated. IL-35 level was measured by ELISA. Peripheral CD14monocytes were purified, and the IL-35 receptor subunits (IL-12Rβ2 and gp130 mRNA) relative levels were semi-quantified by real-time PCR. CD14monocytes were stimulated with IL-35, and were cultured in direct contact or indirect contact with human umbilical vein endothelial cells (HUVEC). Cytokines and granzyme B secretion in the supernatants was measured by ELISA. The percentage of HUVEC death was calculated by measuring lactate dehydrogenase level. The difference of the above indicators were compared between the CHF group and the HC group. The age for the CHF group was (59.4±12.1) years, and 58.1% (43 cases) of them were males. The age for the HC group was (53.9±9.8) years, and 65.5% (19 cases) of them were males. The plasma IL-35 level was higher in the CHF group than the HC group ((22.89±7.58) mg/L vs (16.42±5.47) mg/L, 0.001). The gp130 mRNA relative level was also higher in the CHF group than the HC group (1.07±0.19 vs 0.98±0.15, 0.022). CD14monocytes induced HUVEC death in the CHF group was lower in both direct contact and indirect contact culture system than the HC group (both 0.001). The granzyme B secretion was also lower in the CHF group than the HC group (0.001). The CD14monocytes induced HUVEC death was down-regulated in response to granzyme B inhibition (0.011). Both the CD14monocytes induced HUVEC death and the granzyme B secretion were reduced in response to IL-35 stimulation (both 0.001). CHF patients have the elevated IL-35 expression. IL-35 induces CD14monocytes dysfunction via the inhibition of granzyme B secretion. This process promoted the progression of heart failure.
探讨慢性心力衰竭（CHF）患者白细胞介素-35（IL-35）水平及CD14单核细胞功能的变化。连续纳入2018年7月至2019年6月在郑州大学第一附属医院心内科住院的74例CHF患者以及29例健康对照（HC）。于上午采集20 ml空腹抗凝外周血，分离血浆。采用酶联免疫吸附测定（ELISA）法检测IL-35水平。纯化外周血CD14单核细胞，通过实时聚合酶链反应（PCR）半定量检测IL-35受体亚基（IL-12Rβ2和gp130 mRNA）的相对水平。用IL-35刺激CD14单核细胞，并将其与人类脐静脉内皮细胞（HUVEC）进行直接接触或间接接触培养。采用ELISA法检测上清液中细胞因子和颗粒酶B的分泌情况。通过检测乳酸脱氢酶水平计算HUVEC死亡百分比。比较CHF组和HC组上述指标的差异。CHF组患者年龄为（59.4±12.1）岁，其中男性占58.1%（43例）。HC组患者年龄为（53.9±9.8）岁，其中男性占65.5%（19例）。CHF组血浆IL-35水平高于HC组（（22.89±7.58）mg/L比（16.42±5.47）mg/L，P<0.001）。CHF组gp130 mRNA相对水平也高于HC组（1.07±0.19比0.98±0.15，P=0.022）。在直接接触和间接接触培养系统中，CHF组CD14单核细胞诱导的HUVEC死亡均低于HC组（均P<0.001）。CHF组颗粒酶B分泌也低于HC组（P<0.001）。抑制颗粒酶B后，CD14单核细胞诱导的HUVEC死亡下调（P=0.011）。IL-35刺激后，CD14单核细胞诱导的HUVEC死亡和颗粒酶B分泌均减少（均P<0.001）。CHF患者IL-35表达升高。IL-35通过抑制颗粒酶B分泌诱导CD14单核细胞功能障碍。这一过程促进了心力衰竭的进展。
