Zheng Hong
Department of Outpatient (East), The First Central Hospital of Baoding, Baoding City, China.
Medicine (Baltimore). 2025 Apr 18;104(16):e42104. doi: 10.1097/MD.0000000000042104.
Pneumonia and sepsis are severe diseases with high mortality and recurrence rates globally, especially fatal among immunocompromised patients. The dual regulatory effects of the cytokines Interleukin-10 (IL-10) and interleukin-18 (IL-18) in inflammatory responses have been observed across various diseases. However, their specific mechanisms in pneumonia and sepsis remain unclear. This study aims to explore the expression characteristics and functions of IL-10 and IL-18 in these diseases using bioinformatics approaches. The pneumonia and sepsis dataset GSE218494 was downloaded from the gene expression omnibus database. Differentially expressed genes were identified using the R package "limma," and functional enrichment analyses were performed using gene ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis. Additionally, weighted gene co-expression network analysis was conducted to identify key module genes, and the Search Tool for the Retrieval of Interacting Genes database and Cytoscape software were used to construct a protein-protein interaction network to identify core genes. Further analysis of miRNA targets associated with these core genes was performed to elucidate their potential molecular mechanisms in the diseases. The analysis revealed that IL-10 and IL-18 were downregulated in patients with pneumonia and sepsis, closely associated with poor prognosis. Functional enrichment analysis showed that these genes are primarily involved in biological processes related to inflammation and immune regulation, including the cell cycle, TGF-β signaling pathway, and Jak-STAT signaling pathway. Protein-protein interaction network analysis identified IL-10 and IL-18 as potential key regulatory genes in pneumonia and sepsis. miRNA prediction indicated that several miRNAs are closely associated with the regulation of these genes' expression. IL-10 and IL-18 play critical immunoregulatory roles in the development and progression of pneumonia and sepsis, impacting patient prognosis. These findings provide theoretical support for future IL-10 and IL-18-targeted therapeutic strategies, which may improve clinical outcomes for patients with pneumonia and sepsis.
肺炎和脓毒症是全球范围内死亡率和复发率都很高的严重疾病，在免疫功能低下的患者中尤其致命。细胞因子白细胞介素-10（IL-10）和白细胞介素-18（IL-18）在各种疾病的炎症反应中具有双重调节作用。然而，它们在肺炎和脓毒症中的具体机制仍不清楚。本研究旨在利用生物信息学方法探索IL-10和IL-18在这些疾病中的表达特征和功能。从基因表达综合数据库下载了肺炎和脓毒症数据集GSE218494。使用R包“limma”鉴定差异表达基因，并使用基因本体论、京都基因与基因组百科全书和基因集富集分析进行功能富集分析。此外，进行加权基因共表达网络分析以鉴定关键模块基因，并使用检索相互作用基因数据库的搜索工具和Cytoscape软件构建蛋白质-蛋白质相互作用网络以鉴定核心基因。对与这些核心基因相关的miRNA靶标进行进一步分析，以阐明它们在疾病中的潜在分子机制。分析显示，IL-10和IL-18在肺炎和脓毒症患者中表达下调，与预后不良密切相关。功能富集分析表明，这些基因主要参与与炎症和免疫调节相关的生物学过程，包括细胞周期、TGF-β信号通路和Jak-STAT信号通路。蛋白质-蛋白质相互作用网络分析确定IL-10和IL-18是肺炎和脓毒症中潜在的关键调节基因。miRNA预测表明，几种miRNA与这些基因表达的调节密切相关。IL-10和IL-18在肺炎和脓毒症的发生和发展中发挥关键的免疫调节作用，影响患者预后。这些发现为未来以IL-10和IL-18为靶点的治疗策略提供了理论支持，这可能改善肺炎和脓毒症患者的临床结局。
