Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.

Crosstalk Between Plasma Cytokines, Inflammation, and Liver Damage as a New Strategy to Monitoring NAFLD Progression.
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DOI:
10.3389/fimmu.2021.708959
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发表时间:
2021
影响因子:
7.3
通讯作者:
Gomes JAS
Gomes JAS
中科院分区:
医学2区
文献类型:
--
作者:
Fontes-Cal TCM;Mattos RT;Medeiros NI;Pinto BF;Belchior-Bezerra M;Roque-Souza B;Dutra WO;Ferrari TCA;Vidigal PVT;Faria LC;Couto CA;Gomes JAS

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细胞因子参与了非酒精性脂肪性肝病(NAFLD)的免疫发病机制,但它们与NAFLD进展的临床参数之间的关系仍不清楚。我们使用流式细胞术评估了经活检证实的单纯性脂肪变性(NAFL)和非酒精性脂肪性肝炎(NASH)患者的血浆IL-1β、IL-6、IL-12、TNF和IL-10水平及其与肝功能临床和生化参数的相关性。NASH患者显示出与较低的IL-10/IL-6比率相关的较高水平的IL-6。除了热图在NAFL和NASH组中相似之外,在特征曲线中没有发生同样的情况,NASH患者是IL-12和IL-6的高生产者,而NAFL患者不是所评估的任何细胞因子的高生产者。综合生物标志物网络分析显示,细胞因子与NAFL患者的临床指标有不同程度的相关性,而IL-12、IL-10与NAFL患者的血糖和血脂呈中度和负相关。NASH组IL-12和TNF与一过性弹性成像参数和NAFLD肝纤维化评分呈较强的正相关。这些数据表明,IL-6和IL-10可能在慢性炎症和胰岛素抵抗中起作用,而IL-12和TNF可能参与促进肝损伤和NAFLD进展。这些分子的血浆浓度分析及其与临床参数的相关性可用作监测NAFLD进展和反映NASH发展的新生物标志物。
Cytokines are involved in the immunopathogenesis of nonalcoholic fatty liver disease (NAFLD), but the relationship between them and clinical parameters of NAFLD progression is still unknown. Using flow cytometry, we evaluated the plasma levels of IL-1β, IL-6, IL-12, TNF and IL-10 and their association with clinical and biochemical parameters of liver function during simple steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) in biopsy-proven patients. The NASH patients showed higher levels of IL-6 associated with a lower IL-10/IL-6 ratio. Besides heatmaps were similar in the NAFL and NASH groups, the same did not occur in signature curves, the NASH patients were high producers to IL-12 and IL-6 while the NAFL patients were not high producers of any cytokines evaluated. Integrative biomarker network analysis revealed that cytokines are differently correlated with clinical parameters, while IL-12, IL-10 presented moderate and negative correlations with glycemic and lipid profile in the NAFL group. The NASH group IL-12 and TNF revealed stronger and positive correlations with transient elastography parameters and NAFLD liver fibrosis score. These data suggest that IL-6 and IL-10 might act in chronic inflammation and insulin resistance whereas IL-12 and TNF may be involved in promoting liver damage and NAFLD progression. Plasma concentration analysis of these molecules and their association with clinical parameters can be used as new biomarkers to monitoring NAFLD progression and to reflect NASH development.
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