The critical immunoregulatory roles and molecular mechanisms of IL-10 and IL-18 genes in pneumonia and sepsis

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.