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慢性丙型肝炎和非酒精性脂肪性肝炎中的白细胞介素-23/白细胞介素-17轴——对不同慢性肝病免疫性肝毒性的新认识

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis-New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases.

作者信息

Vujovic Ankica, Isakovic Andjelka M, Misirlic-Dencic Sonja, Juloski Jovan, Mirkovic Milan, Cirkovic Andja, Djelic Marina, Milošević Ivana

机构信息

Clinic for Infectious and Tropical Diseases, University Clinical Center of Serbia, 11 000 Belgrade, Serbia.

Faculty of Medicine, University of Belgrade, 11 000 Belgrade, Serbia.

出版信息

Int J Mol Sci. 2023 Aug 5;24(15):12483. doi: 10.3390/ijms241512483.

Abstract

Considering the relevance of the research of pathogenesis of different liver diseases, we investigated the possible activity of the IL-23/IL-17 axis on the immunohepatotoxicity of two etiologically different chronic liver diseases. A total of 36 chronic hepatitis C (CHC) patients, 16 with (CHC-SF) and 20 without significant fibrosis (CHC-NSF), 19 patients with non-alcoholic steatohepatitis (NASH), and 20 healthy controls (CG) were recruited. Anthropometric, biochemical, and immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed in accordance with standard procedure. Our analysis revealed that a higher concentration of plasma IL-23 was associated with NASH ( = 0.005), and a higher concentration of plasma IL-17A but a lower concentration of plasma IL-10 was associated with CHC in comparison with CG. A lower concentration of plasma IL-10 was specific for CHC-NSF, while a higher concentration of plasma IL-17A was specific for CHC-SF in comparison with CG. CHC-NSF and CHC-SF groups were distinguished from NASH according to a lower concentration of plasma IL-17A. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in comparison with NASH, regardless of the same stage of the liver fibrosis, whereas only IL-17A tissue levels showed a difference between the CHC-NSF and CHC-SF groups, namely, a lower concentration in CHC-NSF in comparison with CHC-SF. In CHC-SF and NASH liver tissue, IL17-A and IL-23 were significantly higher in comparison with plasma. Diagnostic accuracy analysis showed significance only in the concentration of plasma cytokines. Plasma IL-6, IL-17A and IL-23 could be possible markers that could differentiate CHC patients from controls. Plasma IL-23 could be considered a possible biomarker of CHC-NSF patients in comparison with controls, while plasma IL-6 and IL-17-A could be biomarkers of CHC-SF patients in comparison with controls. The most sophisticated difference was between the CHC-SF and CHC-NSF groups in the plasma levels of IL-10, which could make this cytokine a useful biomarker of liver fibrosis.

摘要

鉴于不同肝脏疾病发病机制研究的相关性,我们研究了IL-23/IL-17轴对两种病因不同的慢性肝病免疫肝毒性的可能作用。共招募了36例慢性丙型肝炎(CHC)患者,其中16例伴有显著纤维化(CHC-SF),20例无显著纤维化(CHC-NSF),19例非酒精性脂肪性肝炎(NASH)患者,以及20名健康对照者(CG)。按照标准程序进行人体测量、生化和免疫细胞因子(IL-6、IL-10、IL-17和IL-23)检测。我们的分析显示,血浆IL-23浓度较高与NASH相关(P = 0.005),与CG相比,CHC患者血浆IL-17A浓度较高但IL-10浓度较低。血浆IL-10浓度较低是CHC-NSF所特有的,而与CG相比,血浆IL-17A浓度较高是CHC-SF所特有的。根据血浆IL-17A浓度较低,CHC-NSF和CHC-SF组与NASH相区分。无论肝纤维化处于同一阶段,CHC-NSF组肝组织中IL-17A和IL-23水平均显著低于NASH组,而只有IL-17A组织水平在CHC-NSF和CHC-SF组之间存在差异,即CHC-NSF组低于CHC-SF组。在CHC-SF和NASH肝组织中,IL-17A和IL-23显著高于血浆。诊断准确性分析显示仅血浆细胞因子浓度具有统计学意义。血浆IL-6、IL-17A和IL-23可能是区分CHC患者与对照者的标志物。与对照者相比,血浆IL-23可被视为CHC-NSF患者的可能生物标志物,而与对照者相比,血浆IL-6和IL-17A可作为CHC-SF患者的生物标志物。最显著的差异在于CHC-SF和CHC-NSF组血浆IL-10水平,这可能使该细胞因子成为肝纤维化的有用生物标志物。

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