Pub Date : 2025-11-19DOI: 10.1016/j.cyto.2025.157075
Chao Wang, Yi Cai, Jie Jie
Introduction
Multiple Myeloma (MM) disrupts immune function and causes multisystem damage. Despite treatment advances, the pathogenesis of relapse and resistance remain unclear. This study assesses the causal relationships between immune cell subtypes and MM using Mendelian randomization (MR), explores the mediating role of cytokines, and identifies potential therapeutic targets.
Methods
We employed a two-step MR approach to analyze mediating effects. Sensitivity analyses and Bayesian Weighted Mendelian Randomization (BWMR) were utilized to ensure the accuracy of results and to mitigate pleiotropy and heterogeneity. Additionally, Summary-data-based MR (SMR) was used to identify potential drug targets.
Results
The findings indicate causal effects of 20 immune cell subtypes and three cytokines on MM. SLAM mediated 9.16 % of the effect of CD4+ cells on MM. SMR analysis identified CD4+ and naive CD4+ cells as potential therapeutic targets for MM.
Conclusions
Through two-step MR and SMR analysis, this study reveals the mediating role of SLAM in the impact of CD4+ immune cells on MM and identifies two immune cell drug targets. Inhibiting the KIT gene may enhance the antitumor function of CD4+ T cells, offering new insights and potential strategies for immunotherapy of MM. These findings provide a theoretical basis for understanding the pathophysiology of MM and for developing novel immune-targeted therapies.
{"title":"The role of cytokines in immune cell-mediated multiple myeloma and the identification of therapeutic targets","authors":"Chao Wang, Yi Cai, Jie Jie","doi":"10.1016/j.cyto.2025.157075","DOIUrl":"10.1016/j.cyto.2025.157075","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple Myeloma (MM) disrupts immune function and causes multisystem damage. Despite treatment advances, the pathogenesis of relapse and resistance remain unclear. This study assesses the causal relationships between immune cell subtypes and MM using Mendelian randomization (MR), explores the mediating role of cytokines, and identifies potential therapeutic targets.</div></div><div><h3>Methods</h3><div>We employed a two-step MR approach to analyze mediating effects. Sensitivity analyses and Bayesian Weighted Mendelian Randomization (BWMR) were utilized to ensure the accuracy of results and to mitigate pleiotropy and heterogeneity. Additionally, Summary-data-based MR (SMR) was used to identify potential drug targets.</div></div><div><h3>Results</h3><div>The findings indicate causal effects of 20 immune cell subtypes and three cytokines on MM. SLAM mediated 9.16 % of the effect of CD4<sup>+</sup> cells on MM. SMR analysis identified CD4<sup>+</sup> and naive CD4<sup>+</sup> cells as potential therapeutic targets for MM.</div></div><div><h3>Conclusions</h3><div>Through two-step MR and SMR analysis, this study reveals the mediating role of SLAM in the impact of CD4<sup>+</sup> immune cells on MM and identifies two immune cell drug targets. Inhibiting the <em>KIT</em> gene may enhance the antitumor function of CD4<sup>+</sup> T cells, offering new insights and potential strategies for immunotherapy of MM. These findings provide a theoretical basis for understanding the pathophysiology of MM and for developing novel immune-targeted therapies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157075"},"PeriodicalIF":3.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune inflammatory myopathy characterized by muscle and skin involvement. Myositis-specific autoantibodies (MSAs) define distinct clinical subgroups, yet the underlying inflammatory mechanisms remain unclear. This study aimed to investigate serum cytokine profiles in patients with JDM and their associations with MSA subgroups, clinical features, and laboratory findings.
Methods
Serum levels of interferon (IFN)-α, interleukin (IL)-18, C-X-C motif chemokine ligand 9 (CXCL9), soluble tumor necrosis factor receptor type II (sTNF-RII), and IL-6 were measured in patients with JDM using enzyme-linked immunosorbent assays. Results were compared with clinical symptoms and laboratory parameters in each MSA subgroup. To explore cytokine-based disease classification, principal component analysis (PCA) and hierarchical clustering were performed.
Results
Serum cytokine profiles differed across MSA subgroups. Patients with anti-melanoma differentiation-associated protein 5 (MDA5) antibodies exhibited significantly elevated IFN-α, IL-18, and CXCL9 levels, correlating with lung involvement. Patients with anti-nuclear matrix protein 2 (NXP2) antibodies demonstrated increased sTNF-RII and IL-6 levels, which were strongly associated with muscle injury markers. Patients with anti-transcriptional intermediary factor 1 gamma (TIF1γ) antibodies exhibited slight increase in cytokine levels, suggesting a different inflammatory pathway. PCA and clustering analysis further supported the cytokine-based classification of JDM.
Conclusions
Distinct cytokine signatures in the JDM subgroups underscore their role in disease heterogeneity and clinical presentation. These findings support cytokine profiling as a potential tool for patient classification and personalized treatment.
{"title":"Distinct cytokine signature in juvenile dermatomyositis: linking myositis-specific antibodies and clinical manifestations","authors":"Shuya Kaneko , Mao Mizuta , Maho Hatano , Asami Shimbo , Hitoshi Irabu , Reiko Yatabe , Keiji Akamine , Yuko Sugita , Kunio Hashimoto , Yuichi Yamasaki , Yasuo Nakagishi , Masaaki Mori , Masatoshi Takagi , Masaki Shimizu","doi":"10.1016/j.cyto.2025.157070","DOIUrl":"10.1016/j.cyto.2025.157070","url":null,"abstract":"<div><h3>Objectives</h3><div>Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune inflammatory myopathy characterized by muscle and skin involvement. Myositis-specific autoantibodies (MSAs) define distinct clinical subgroups, yet the underlying inflammatory mechanisms remain unclear. This study aimed to investigate serum cytokine profiles in patients with JDM and their associations with MSA subgroups, clinical features, and laboratory findings.</div></div><div><h3>Methods</h3><div>Serum levels of interferon (IFN)-α, interleukin (IL)-18, C-X-C motif chemokine ligand 9 (CXCL9), soluble tumor necrosis factor receptor type II (sTNF-RII), and IL-6 were measured in patients with JDM using enzyme-linked immunosorbent assays. Results were compared with clinical symptoms and laboratory parameters in each MSA subgroup. To explore cytokine-based disease classification, principal component analysis (PCA) and hierarchical clustering were performed.</div></div><div><h3>Results</h3><div>Serum cytokine profiles differed across MSA subgroups. Patients with anti-melanoma differentiation-associated protein 5 (MDA5) antibodies exhibited significantly elevated IFN-α, IL-18, and CXCL9 levels, correlating with lung involvement. Patients with anti-nuclear matrix protein 2 (NXP2) antibodies demonstrated increased sTNF-RII and IL-6 levels, which were strongly associated with muscle injury markers. Patients with anti-transcriptional intermediary factor 1 gamma (TIF1γ) antibodies exhibited slight increase in cytokine levels, suggesting a different inflammatory pathway. PCA and clustering analysis further supported the cytokine-based classification of JDM.</div></div><div><h3>Conclusions</h3><div>Distinct cytokine signatures in the JDM subgroups underscore their role in disease heterogeneity and clinical presentation. These findings support cytokine profiling as a potential tool for patient classification and personalized treatment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157070"},"PeriodicalIF":3.7,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145518358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-12DOI: 10.1016/j.cyto.2025.157072
Xingzhi Guo , Peng Tang , Junchi He , Rui Li
Background
Research has suggested a potential link between colony-stimulating factors (CSFs) and Alzheimer's disease (AD), but the findings have been inconsistent, and the causal relationship remains uncertain.
Methods
We performed a Mendelian Randomization (MR) analysis to explore the association between blood levels of CSFs and their receptors with AD and its biomarkers. The study utilized summary-level data on blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and their receptors from deCODE. Data on AD were sourced from the International Genomics of Alzheimer's Project (IGAP), UK Biobank (UKB), and FinnGen, while cerebrospinal fluid p-Tau and β-amyloid levels were from the largest GWAS currently available. Additional summary-level data on amyloid PET imaging and AD progression from ADNI and the Knight-ADRC were also included.
Results
Genetically predicted one standard deviation increase in blood G-CSF was associated with a higher risk of AD across three datasets (IGAP: OR = 1.35, 95 %CI = 1.15–1.57, P < 0.001; IGAP+UKB: OR = 1.27, 95 %CI = 1.12–1.43, P < 0.001; FinnGen: OR = 1.43, 95 %CI = 1.26–1.61, P < 0.001), but not AD progression. Elevated blood G-CSF levels were inversely related to β-amyloid levels (β = −0.14, 95 %CI = -0.19 to −0.09, P < 0.001) and positively associated with p-Tau levels (β = 0.08, 95 %CI = 0.03 to 0.14, P = 0.001) in cerebrospinal fluid. Furthermore, genetically predicted blood G-CSF levels were positively associated with amyloid PET imaging in the brain (β = 0.10, 95 % CI: 0.06 to 0.14, P < 0.001). However, no significant associations were found between blood levels of other CSFs, and their receptors and AD risk. In contrast, there was little evidence supporting the impact of AD on CSFs levels. The multivariable MR analysis showed that the association between G-CSF and AD, along with its biomarkers, disappeared after adjusting for C-reactive protein levels, but not for neutrophil count.
Conclusion
These findings indicate a harmful role of G-CSF in the development of AD, primarily driven by inflammatory responses rather than neutrophil counts. Therefore, interventions targeting AD through CSFs, especially G-CSF, should be cautiously approached.
背景：研究表明集落刺激因子（csf）与阿尔茨海默病（AD）之间存在潜在联系，但研究结果不一致，因果关系仍不确定。方法：我们采用孟德尔随机化（Mendelian Randomization， MR）分析，探讨血中csf及其受体水平与AD及其生物标志物之间的关系。该研究利用了来自deCODE的粒细胞集落刺激因子（G-CSF）、粒细胞-巨噬细胞集落刺激因子、巨噬细胞集落刺激因子及其受体的血液水平的汇总数据。AD的数据来自国际阿尔茨海默氏症基因组计划（IGAP）、英国生物银行（UKB）和FinnGen，脑脊液p-Tau和β-淀粉样蛋白水平来自目前最大的GWAS。ADNI和Knight-ADRC的淀粉样蛋白PET成像和AD进展的其他汇总数据也包括在内。结果：基因预测在三个数据集中，血液中G-CSF的一个标准差增加与AD的高风险相关（IGAP: OR = 1.35, 95% CI = 1.15-1.57， P）。结论：这些发现表明G-CSF在AD的发展中具有有害作用，主要由炎症反应而不是中性粒细胞计数驱动。因此，通过csf，特别是G-CSF靶向AD的干预措施应谨慎对待。
{"title":"Dissecting the effect of blood colony-stimulating factors and receptors on Alzheimer's disease: the role of myeloid traits and inflammation","authors":"Xingzhi Guo , Peng Tang , Junchi He , Rui Li","doi":"10.1016/j.cyto.2025.157072","DOIUrl":"10.1016/j.cyto.2025.157072","url":null,"abstract":"<div><h3>Background</h3><div>Research has suggested a potential link between colony-stimulating factors (CSFs) and Alzheimer's disease (AD), but the findings have been inconsistent, and the causal relationship remains uncertain.</div></div><div><h3>Methods</h3><div>We performed a Mendelian Randomization (MR) analysis to explore the association between blood levels of CSFs and their receptors with AD and its biomarkers. The study utilized summary-level data on blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, and their receptors from deCODE. Data on AD were sourced from the International Genomics of Alzheimer's Project (IGAP), UK Biobank (UKB), and FinnGen, while cerebrospinal fluid p-Tau and β-amyloid levels were from the largest GWAS currently available. Additional summary-level data on amyloid PET imaging and AD progression from ADNI and the Knight-ADRC were also included.</div></div><div><h3>Results</h3><div>Genetically predicted one standard deviation increase in blood G-CSF was associated with a higher risk of AD across three datasets (IGAP: OR = 1.35, 95 %CI = 1.15–1.57, <em>P</em> < 0.001; IGAP+UKB: OR = 1.27, 95 %CI = 1.12–1.43, P < 0.001; FinnGen: OR = 1.43, 95 %CI = 1.26–1.61, <em>P</em> < 0.001), but not AD progression. Elevated blood G-CSF levels were inversely related to β-amyloid levels (β = −0.14, 95 %CI = -0.19 to −0.09, P < 0.001) and positively associated with p-Tau levels (β = 0.08, 95 %CI = 0.03 to 0.14, <em>P</em> = 0.001) in cerebrospinal fluid. Furthermore, genetically predicted blood G-CSF levels were positively associated with amyloid PET imaging in the brain (β = 0.10, 95 % CI: 0.06 to 0.14, <em>P</em> < 0.001). However, no significant associations were found between blood levels of other CSFs, and their receptors and AD risk. In contrast, there was little evidence supporting the impact of AD on CSFs levels. The multivariable MR analysis showed that the association between G-CSF and AD, along with its biomarkers, disappeared after adjusting for C-reactive protein levels, but not for neutrophil count.</div></div><div><h3>Conclusion</h3><div>These findings indicate a harmful role of G-CSF in the development of AD, primarily driven by inflammatory responses rather than neutrophil counts. Therefore, interventions targeting AD through CSFs, especially G-CSF, should be cautiously approached.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157072"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.cyto.2025.157071
Na Zhao , Mayinuer Maimaiti , Hongyan Li
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease, and the association between the fibronectin-related genes (FRGs) and MS is unclear. We aimed to clarify the molecular mechanism and causality of FRGs in MS by single-cell combining Mendelian randomization (MR) analysis. The cell types identified by single-cell analysis with GSE193770 dataset were sorted into high- and low-expression groups based on FRG levels. According to differentially expressed genes from key cells, MR was employed to obtain key genes and their causal relationships. Additionally, immune infiltration analysis and functional enrichment were performed to explore the significance of key genes, with RT-qPCR validating their expression. Six cell types were identified, with natural killer (NK) cells being pivotal. Four key genes were revealed from MR: CAT, RGS10, S100A10, and CD247. Univariable MR showed CAT and RGS10 as protective factors, while S100A10 and CD247 were risk factors. Multivariable MR further emphasized CD247's significance. Expression validation using the GSE41850 dataset and RT-qPCR confirmed underexpression of CAT and CD247 in MS samples, and overexpression of S100A10. Immune infiltration analysis showed significant positive correlations between CD247 and Tregs, resting CD4 memory T cells, and T follicular helper cells, while CAT showed significant negative correlations with activated and resting NK cells. This study explored the causal relationship between the key genes CAT, RGS10, S100A10, and CD247 and MS progression and provided novel perspectives into the application of FRGs for the treatment and prognosis of MS.
{"title":"Combining single-cell analysis and Mendelian randomization to elucidate the molecular mechanisms of fibronectin-related genes in multiple sclerosis","authors":"Na Zhao , Mayinuer Maimaiti , Hongyan Li","doi":"10.1016/j.cyto.2025.157071","DOIUrl":"10.1016/j.cyto.2025.157071","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disease, and the association between the fibronectin-related genes (FRGs) and MS is unclear. We aimed to clarify the molecular mechanism and causality of FRGs in MS by single-cell combining Mendelian randomization (MR) analysis. The cell types identified by single-cell analysis with GSE193770 dataset were sorted into high- and low-expression groups based on FRG levels. According to differentially expressed genes from key cells, MR was employed to obtain key genes and their causal relationships. Additionally, immune infiltration analysis and functional enrichment were performed to explore the significance of key genes, with RT-qPCR validating their expression. Six cell types were identified, with natural killer (NK) cells being pivotal. Four key genes were revealed from MR: <em>CAT</em>, <em>RGS10</em>, <em>S100A10</em>, and <em>CD247</em>. Univariable MR showed <em>CAT</em> and <em>RGS10</em> as protective factors, while <em>S100A10</em> and <em>CD247</em> were risk factors. Multivariable MR further emphasized <em>CD247</em>'s significance. Expression validation using the GSE41850 dataset and RT-qPCR confirmed underexpression of <em>CAT</em> and <em>CD247</em> in MS samples, and overexpression of <em>S100A10</em>. Immune infiltration analysis showed significant positive correlations between <em>CD247</em> and Tregs, resting CD4 memory T cells, and T follicular helper cells, while <em>CAT</em> showed significant negative correlations with activated and resting NK cells. This study explored the causal relationship between the key genes <em>CAT</em>, <em>RGS10</em>, <em>S100A10</em>, and <em>CD247</em> and MS progression and provided novel perspectives into the application of FRGs for the treatment and prognosis of MS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157071"},"PeriodicalIF":3.7,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.cyto.2025.157069
Mengxu Yi , Ying Zhu , Mingyan Wang, Xingyu Mo, Yan Lu, Yu Qiao, Hongyan Lu
This study investigates the critical function of interferon regulatory factor 4 (IRF4) during bronchopulmonary dysplasia (BPD) progression by regulating alveolar macrophages (AMs) polarization and phagocytic function. We developed IRF4 knockout mice using CRISPR/Cas9 technology and established an animal model for neonatal bronchopulmonary dysplasia (BPD) by hyperoxia exposure. Lung tissue pathology was analyzed by Hematoxylin and eosin staining (HE). The concentrations of TNF-α, IL-1β, IL-10, and TGF-β were ascertained by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to investigate M1/M2 macrophage polarization in bronchoalveolar lavage fluid (BALF) and lung tissue, while Western blotting and quantitative real-time PCR (qRT-PCR) were employed to detect IRF4, iNOS, and Arg-1 protein and mRNA expression. At cellular level, we silenced IRF4 in murine alveolar macrophage cell lines using IRF4 siRNA to investigate its effect on inflammatory cytokine secretion, polarization, and phagocytic function. To assess the effect of IRF4 on alveolar macrophage phagocytosis after hyperoxia, we utilized flow cytometry to ascertain the mean fluorescence intensity of engulfed fluorescent microspheres and fluorescence microscopy to quantify phagocytic cells. Hyperoxia-exposed mice showed markedly upregulated IRF4 expression, increased M1 macrophage and iNOS levels, and decreased M2 macrophages and Arg-1 expression. This cytokine shift was characterized by a marked upregulation of inflammatory factors such as TNF-α and IL-1β, accompanied by a notable decline in anti-inflammatory factors encompassing IL-10 and TGF-β, indicating an imbalance towards a pro-inflammatory state. IRF4 knockout or siRNA-mediated silencing attenuated the inflammatory response, promoting M2 macrophage differentiation while suppressing M1 differentiation. Phagocytic assays showed that hyperoxia impaired the phagocytic activity of AMs, while transfection of IRF4 siRNA restored the phagocytic activity of macrophage. IRF4 functions as a crucial regulator in the progression of hyperoxia-induced bronchopulmonary dysplasia, exerting its effects by influencing the polarization state and phagocytic function of alveolar macrophages. Deletion of IRF4 promotes an M2-dominant anti-inflammatory response, attenuates hyperoxia-induced inflammation, and increases the phagocytosis capacity of macrophages.
{"title":"IRF4 exacerbates pulmonary inflammation in bronchopulmonary dysplasia mice model by regulating macrophage polarization and phagocytosis","authors":"Mengxu Yi , Ying Zhu , Mingyan Wang, Xingyu Mo, Yan Lu, Yu Qiao, Hongyan Lu","doi":"10.1016/j.cyto.2025.157069","DOIUrl":"10.1016/j.cyto.2025.157069","url":null,"abstract":"<div><div>This study investigates the critical function of interferon regulatory factor 4 (IRF4) during bronchopulmonary dysplasia (BPD) progression by regulating alveolar macrophages (AMs) polarization and phagocytic function. We developed IRF4 knockout mice using CRISPR/Cas9 technology and established an animal model for neonatal bronchopulmonary dysplasia (BPD) by hyperoxia exposure. Lung tissue pathology was analyzed by Hematoxylin and eosin staining (HE). The concentrations of TNF-α, IL-1β, IL-10, and TGF-β were ascertained by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to investigate M1/M2 macrophage polarization in bronchoalveolar lavage fluid (BALF) and lung tissue, while Western blotting and quantitative real-time PCR (qRT-PCR) were employed to detect IRF4, iNOS, and Arg-1 protein and mRNA expression. At cellular level, we silenced IRF4 in murine alveolar macrophage cell lines using IRF4 siRNA to investigate its effect on inflammatory cytokine secretion, polarization, and phagocytic function. To assess the effect of IRF4 on alveolar macrophage phagocytosis after hyperoxia, we utilized flow cytometry to ascertain the mean fluorescence intensity of engulfed fluorescent microspheres and fluorescence microscopy to quantify phagocytic cells. Hyperoxia-exposed mice showed markedly upregulated IRF4 expression, increased M1 macrophage and iNOS levels, and decreased M2 macrophages and Arg-1 expression. This cytokine shift was characterized by a marked upregulation of inflammatory factors such as TNF-α and IL-1β, accompanied by a notable decline in anti-inflammatory factors encompassing IL-10 and TGF-β, indicating an imbalance towards a pro-inflammatory state. IRF4 knockout or siRNA-mediated silencing attenuated the inflammatory response, promoting M2 macrophage differentiation while suppressing M1 differentiation. Phagocytic assays showed that hyperoxia impaired the phagocytic activity of AMs, while transfection of IRF4 siRNA restored the phagocytic activity of macrophage. IRF4 functions as a crucial regulator in the progression of hyperoxia-induced bronchopulmonary dysplasia, exerting its effects by influencing the polarization state and phagocytic function of alveolar macrophages. Deletion of IRF4 promotes an M2-dominant anti-inflammatory response, attenuates hyperoxia-induced inflammation, and increases the phagocytosis capacity of macrophages.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157069"},"PeriodicalIF":3.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1016/j.cyto.2025.157066
Ilaria Schiavoni , Anita Muglia , Pasqualina Leone , Eleonora Olivetta , Sergio Abrignani , Davide Anzà , Alessandra Bandera , Francesca Fortunato , Andrea Gori , Renata Grifantini , Tiziana Lazzarotto , Vittorio Lodi , Rosa Prato , Vincenzo Restivo , Anna Teresa Palamara , Paola Stefanelli , Giorgio Fedele , the COVAC-3 Study Group
The early innate immune response to vaccination plays a crucial role in shaping adaptive immunity and long-term protection. In this study, we investigated the early cytokine response to COVID-19 and flu vaccination and its association with mid-term humoral immunity. Twenty-nine healthcare workers (HCWs) who received the monovalent SARS-CoV-2 XBB.1.5 mRNA vaccine along with the seasonal quadrivalent inactivated influenza vaccine were enrolled. Serum samples were collected at baseline (T0), five days (T1), three months (T2), and six months (T3) post-vaccination. The levels of seven innate cytokines and chemokines were quantified at T0 and T1, while anti-trimeric spike (S) IgG titers were measured at T0, T2 and T3. Our analysis revealed a significant increase in CXCL10, TNF-α, and IL-6 at T1, whereas CCL3 and IL-8 mean levels remained unchanged. Spearman's correlation analysis showed a coordinated activation of inflammatory mediators, with IL-6 and IL-8 exhibiting the strongest correlation. Notably, early cytokine responses were associated with humoral immunity, as IL-6 and IL-8 levels at T1 were negatively correlated with anti-trimeric S IgG titers at T2 and T3. These findings suggest that early inflammatory cytokine increases may limit the persistence of vaccine-induced antibody response.
对疫苗接种的早期先天免疫反应在形成适应性免疫和长期保护中起着至关重要的作用。在这项研究中，我们研究了COVID-19和流感疫苗接种的早期细胞因子反应及其与中期体液免疫的关系。29名卫生保健工作者（HCWs）接受了单价SARS-CoV-2 XBB.1.5 mRNA疫苗和季节性四价灭活流感疫苗。在接种后基线（T0）、5天（T1）、3个月（T2）和6个月（T3）采集血清样本。在T0和T1时测定7种先天细胞因子和趋化因子水平，在T0、T2和T3时测定抗三聚体spike (S) IgG滴度。我们的分析显示，CXCL10、TNF-α和IL-6在T1时显著增加，而CCL3和IL-8的平均水平保持不变。Spearman相关分析显示炎症介质协同激活，其中IL-6和IL-8相关性最强。值得注意的是，早期的细胞因子反应与体液免疫相关，因为T1时的IL-6和IL-8水平与T2和T3时的抗三聚体S IgG滴度呈负相关。这些发现表明，早期炎症细胞因子的增加可能会限制疫苗诱导的抗体反应的持久性。
{"title":"IL-6 and IL-8 elevations after co-administration of COVID-19 and influenza vaccines are associated with lower anti-spike IgG titers at three and six months post-vaccination","authors":"Ilaria Schiavoni , Anita Muglia , Pasqualina Leone , Eleonora Olivetta , Sergio Abrignani , Davide Anzà , Alessandra Bandera , Francesca Fortunato , Andrea Gori , Renata Grifantini , Tiziana Lazzarotto , Vittorio Lodi , Rosa Prato , Vincenzo Restivo , Anna Teresa Palamara , Paola Stefanelli , Giorgio Fedele , the COVAC-3 Study Group","doi":"10.1016/j.cyto.2025.157066","DOIUrl":"10.1016/j.cyto.2025.157066","url":null,"abstract":"<div><div>The early innate immune response to vaccination plays a crucial role in shaping adaptive immunity and long-term protection. In this study, we investigated the early cytokine response to COVID-19 and flu vaccination and its association with mid-term humoral immunity. Twenty-nine healthcare workers (HCWs) who received the monovalent SARS-CoV-2 XBB.1.5 mRNA vaccine along with the seasonal quadrivalent inactivated influenza vaccine were enrolled. Serum samples were collected at baseline (T0), five days (T1), three months (T2), and six months (T3) post-vaccination. The levels of seven innate cytokines and chemokines were quantified at T0 and T1, while anti-trimeric spike (S) IgG titers were measured at T0, T2 and T3. Our analysis revealed a significant increase in CXCL10, TNF-α, and IL-6 at T1, whereas CCL3 and IL-8 mean levels remained unchanged. Spearman's correlation analysis showed a coordinated activation of inflammatory mediators, with IL-6 and IL-8 exhibiting the strongest correlation. Notably, early cytokine responses were associated with humoral immunity, as IL-6 and IL-8 levels at T1 were negatively correlated with anti-trimeric S IgG titers at T2 and T3. These findings suggest that early inflammatory cytokine increases may limit the persistence of vaccine-induced antibody response.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157066"},"PeriodicalIF":3.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-06DOI: 10.1016/j.cyto.2025.157067
Xiaohuan Zhao , Jianfeng Luo , Xiaoxu Huang , Shiming Wang , Hui Cao , Wenjia Liu , Zhaoyu Xiang
Objective
Retinopathy, a common microvascular complication frequently associated with diabetes and systemic inflammation, has been increasingly linked to elevated mortality risk. At the same time, serum C-reactive protein (CRP), albumin (ALB), or CRP/ALB ratio (CAR) was associated with systemic inflammation and mortality risk. The risk of all-cause death in patients with retinopathy increased by 2–4 times. This study aimed to investigate whether CRP, ALB or CAR was associated with all-cause mortality in participants of retinopathy.
Methods
This study included 677 patients with retinopathy in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Associations between CRP, ALB, or CAR and all-cause mortality were assessed. Weighted Cox proportional hazard regression models and Kaplan-Meier curves facilitated the evaluation in both univariable and multivariable models (adjusted for gender, age, BMI, race/ethnicity, marital status, education level, smoking status, drinking habit, family income-to-poverty ratio, patient history of heart attack, stroke, diabetes, and hypertension). Data analysis was conducted from January 1, 2023 to June 30, 2023.
Results
Participants with retinopathy showed a higher mortality risk compared to those without retinopathy, even after adjustments for multiple variables (HRs of 1.450 [95 % CI, 1.249–1.683]). Among 677 participants with retinopathy, the mean baseline age was 62.34 years, and 260 (38.4 %) died over an average follow-up of 126 months. The average serum levels of CRP, ALB, and CAR were 5.27 mg/L, 41.24 g/L, and 0.13, respectively. Elevated concentrations of CRP or CAR were associated with an increased mortality risk (HRs of 1.473 [95 % CI, 1.013–2.143] and 1.638 [95 % CI, 1.132–2.370], respectively). Conversely, a higher ALB level was associated with reduced all-cause mortality (HR of 0.655; 95 % CI, 0.464–0.925). Similarly, higher CRP and CAR, as well as lower ALB, were associated with higher all-cause mortality in people with diabetes retinopathy.
Conclusions
The levels of CRP, ALB, and CAR were predictive of subsequent all-cause mortality in individuals with retinopathy. Elevated levels of CRP and CAR were correlated with an increased mortality risk, while decreased levels of ALB were associated with an enhanced risk of mortality.
{"title":"C-reactive protein and albumin: Examining associations with all-cause mortality risk among adults with retinopathy in NHANES","authors":"Xiaohuan Zhao , Jianfeng Luo , Xiaoxu Huang , Shiming Wang , Hui Cao , Wenjia Liu , Zhaoyu Xiang","doi":"10.1016/j.cyto.2025.157067","DOIUrl":"10.1016/j.cyto.2025.157067","url":null,"abstract":"<div><h3>Objective</h3><div>Retinopathy, a common microvascular complication frequently associated with diabetes and systemic inflammation, has been increasingly linked to elevated mortality risk. At the same time, serum C-reactive protein (CRP), albumin (ALB), or CRP/ALB ratio (CAR) was associated with systemic inflammation and mortality risk. The risk of all-cause death in patients with retinopathy increased by 2–4 times. This study aimed to investigate whether CRP, ALB or CAR was associated with all-cause mortality in participants of retinopathy.</div></div><div><h3>Methods</h3><div>This study included 677 patients with retinopathy in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2008. Associations between CRP, ALB, or CAR and all-cause mortality were assessed. Weighted Cox proportional hazard regression models and Kaplan-Meier curves facilitated the evaluation in both univariable and multivariable models (adjusted for gender, age, BMI, race/ethnicity, marital status, education level, smoking status, drinking habit, family income-to-poverty ratio, patient history of heart attack, stroke, diabetes, and hypertension). Data analysis was conducted from January 1, 2023 to June 30, 2023.</div></div><div><h3>Results</h3><div>Participants with retinopathy showed a higher mortality risk compared to those without retinopathy, even after adjustments for multiple variables (HRs of 1.450 [95 % CI, 1.249–1.683]). Among 677 participants with retinopathy, the mean baseline age was 62.34 years, and 260 (38.4 %) died over an average follow-up of 126 months. The average serum levels of CRP, ALB, and CAR were 5.27 mg/L, 41.24 g/L, and 0.13, respectively. Elevated concentrations of CRP or CAR were associated with an increased mortality risk (HRs of 1.473 [95 % CI, 1.013–2.143] and 1.638 [95 % CI, 1.132–2.370], respectively). Conversely, a higher ALB level was associated with reduced all-cause mortality (HR of 0.655; 95 % CI, 0.464–0.925). Similarly, higher CRP and CAR, as well as lower ALB, were associated with higher all-cause mortality in people with diabetes retinopathy.</div></div><div><h3>Conclusions</h3><div>The levels of CRP, ALB, and CAR were predictive of subsequent all-cause mortality in individuals with retinopathy. Elevated levels of CRP and CAR were correlated with an increased mortality risk, while decreased levels of ALB were associated with an enhanced risk of mortality.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157067"},"PeriodicalIF":3.7,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.cyto.2025.157068
Huijie Huang , Guojun Liang , Yaozong He , Hongyu Wang , Xiaowen Lin , Ziling Zhao , Enyu Liang , Yunxiu Wang , Jian-xin Peng , Hong-wei Sun , Min He
Triptolide (TPT) is a natural compound in herbal remedies with anti-inflammatory and anti-tumor properties. The study aimed to investigate the therapeutic effect of triptolide treatment on Myeloid-derived suppressor cells (MDSCs) in Hepatocellular Carcinoma (HCC). Single-cell transcriptomic profiling of liver tumor biopsies identified (Colony-Stimulating Factor 1 Receptor) CSF1R+ MDSCs as a distinct MDSCs lineage in HCC patients, which exhibited a positive correlation with the severity of HCC. Flow cytometric analysis confirmed CSF1R+ MDSCs were enriched in the peripheral blood and tumor tissue of HCC patients. Elevated CSF1R expression were highly expressed on the polymorphonuclear-MDSCs (PMN-MDSCs) subset specifically. Notably, PERK-mediated endoplasmic reticulum (ER) stress activation contributed to CSF1R induction, as evidenced by inhibiting the activities of PERK, but not IRE1α or ATF6, successfully attenuated the frequency of CSF1R+ MDSCs. Moreover, TPT dose-dependently diminished MDSCs and CSF1R+ MDSCs frequencies, alongside with alleviating the immunosuppressive capability on T cell proliferation. Further investigation revealed TPT treatment suppressed phosphorylation of PERK, as well as the protein levels of ATF4 and C/EBPβ. Our results underscore the role of ER stress-induced CSF1R expression in driving HCC disease progression by promoting the immunosuppressive effects of MDSCs, and identify CSF1R as a promising immunosuppressive target of TPT in HCC therapy.
{"title":"Triptolide impacts CSF1R expression andreprograms the suppressive function of myeloid-derived suppressor cells via targeting the ER stress pathway","authors":"Huijie Huang , Guojun Liang , Yaozong He , Hongyu Wang , Xiaowen Lin , Ziling Zhao , Enyu Liang , Yunxiu Wang , Jian-xin Peng , Hong-wei Sun , Min He","doi":"10.1016/j.cyto.2025.157068","DOIUrl":"10.1016/j.cyto.2025.157068","url":null,"abstract":"<div><div>Triptolide (TPT) is a natural compound in herbal remedies with anti-inflammatory and anti-tumor properties. The study aimed to investigate the therapeutic effect of triptolide treatment on Myeloid-derived suppressor cells (MDSCs) in Hepatocellular Carcinoma (HCC). Single-cell transcriptomic profiling of liver tumor biopsies identified (Colony-Stimulating Factor 1 Receptor) CSF1R<sup>+</sup> MDSCs as a distinct MDSCs lineage in HCC patients, which exhibited a positive correlation with the severity of HCC. Flow cytometric analysis confirmed CSF1R<sup>+</sup> MDSCs were enriched in the peripheral blood and tumor tissue of HCC patients. Elevated CSF1R expression were highly expressed on the polymorphonuclear-MDSCs (PMN-MDSCs) subset specifically. Notably, PERK-mediated endoplasmic reticulum (ER) stress activation contributed to CSF1R induction, as evidenced by inhibiting the activities of PERK, but not IRE1α or ATF6, successfully attenuated the frequency of CSF1R<sup>+</sup> MDSCs. Moreover, TPT dose-dependently diminished MDSCs and CSF1R<sup>+</sup> MDSCs frequencies, alongside with alleviating the immunosuppressive capability on T cell proliferation. Further investigation revealed TPT treatment suppressed phosphorylation of PERK, as well as the protein levels of ATF4 and C/EBPβ. Our results underscore the role of ER stress-induced CSF1R expression in driving HCC disease progression by promoting the immunosuppressive effects of MDSCs, and identify CSF1R as a promising immunosuppressive target of TPT in HCC therapy.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157068"},"PeriodicalIF":3.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.cyto.2025.157065
Dongmei Xiao , Tong Kong , Tinghui Wang , Hua Huang , Wen Qin , Baojing Zhao , Haibo Chen , Xiudi Wu , Kaizhe Wang , Jianping Zheng
Objective
Given the constraints inherent in current biomarkers and renal biopsy techniques for lupus nephritis (LN), this exploratory investigation was conducted to identify novel serum protein expression profiles through proximity extension immunoassay (PEA, Olink) in patients experiencing initial-onset LN for early identification of LN.
Methods
The PEA immunoassay was utilized to quantify serum concentrations of ninety-two inflammation-associated proteins among individuals with initial-onset LN (diagnosed concurrently with systemic lupus erythematosus (SLE), n = 23), patients with initial-onset non-LN manifestations (limited to cutaneous and musculoskeletal symptoms, specifically lupus arthritis (LA), n = 21), and age-matched healthy controls (HC, n = 22). Simultaneously, baseline clinical data were collected from the study population. Subsequently, machine-learning-based statistical modeling was employed to uncover prospective biomarkers indicative of initial-onset LN.
Results
A sum of 36 serum proteins was found to be differentially expressed in initial-onset LN relative to HC, comprising 25 upregulated and 11 downregulated proteins. Notably, transforming growth factor beta-1 proprotein, C-X-C motif chemokine 5, interleukin-15 receptor subunit alpha (IL-15RA), and C-X-C motif chemokine 11 were included in the final predictive model, achieving a sensitivity of 91.67 % and a specificity of 95.24 %. Compared with LA patients, 12 proteins were differentially regulated in the LN group, including 11 downregulated and 1 upregulated protein. Among these, Oncostatin-M, CC motif chemokine 28, Fibroblast growth factor 19, IL-15RA, leukemia inhibitory factor, neurotrophin-3, and TNF-like weak inducer of apoptosis were incorporated into a model yielding a sensitivity of 74.07 % and specificity of 82.35 %.
Conclusion
The application of highly sensitive PEA profiling facilitated the identification of distinct serum protein signatures across SLE, initial-onset LN, and LA, uncovering multiple novel protein candidates. These promising biomarkers, whose precise role and predictive potential within the context of SLE merit further validation.
考虑到目前狼疮性肾炎（LN）的生物标志物和肾活检技术固有的局限性，本探索性研究通过近距离延伸免疫分析法（PEA, Olink）在初发性LN患者中鉴定新的血清蛋白表达谱，以早期识别LN。方法：采用PEA免疫分析法，对首发LN患者（同时诊断为系统性红斑狼疮（SLE）， n = 23）、首发非LN患者（仅限于皮肤和肌肉骨骼症状，特别是狼疮关节炎（LA）， n = 21）和年龄匹配的健康对照组（HC, n = 22）的92种炎症相关蛋白的血清浓度进行定量分析。同时，从研究人群中收集基线临床数据。随后，采用基于机器学习的统计模型来发现指示初始性LN的前瞻性生物标志物。结果36种血清蛋白在初发LN中与HC有差异表达，其中25种表达上调，11种表达下调。值得注意的是，最终的预测模型包括转化生长因子β -1蛋白、C-X-C基序趋化因子5、白介素-15受体亚单位α (IL-15RA)和C-X-C基序趋化因子11，灵敏度为91.67%，特异性为95.24%。与LA患者相比，LN组有12个蛋白发生差异调节，其中11个蛋白下调，1个蛋白上调。其中，Oncostatin-M、CC motif趋化因子28、成纤维细胞生长因子19、IL-15RA、白血病抑制因子、神经营养因子-3和tnf样细胞凋亡弱诱导剂被纳入模型，敏感性为74.07%，特异性为82.35%。高灵敏度PEA分析的应用有助于识别SLE、初发LN和LA的不同血清蛋白特征，揭示多种新的候选蛋白。这些有前景的生物标志物，其在SLE背景下的精确作用和预测潜力值得进一步验证。
{"title":"Serum protein profiles in lupus nephritis associated with initial-onset systemic lupus erythematosus: Characterization through PEA immunoassay and preliminary development of predictive model","authors":"Dongmei Xiao , Tong Kong , Tinghui Wang , Hua Huang , Wen Qin , Baojing Zhao , Haibo Chen , Xiudi Wu , Kaizhe Wang , Jianping Zheng","doi":"10.1016/j.cyto.2025.157065","DOIUrl":"10.1016/j.cyto.2025.157065","url":null,"abstract":"<div><h3>Objective</h3><div>Given the constraints inherent in current biomarkers and renal biopsy techniques for lupus nephritis (LN), this exploratory investigation was conducted to identify novel serum protein expression profiles through proximity extension immunoassay (PEA, Olink) in patients experiencing initial-onset LN for early identification of LN.</div></div><div><h3>Methods</h3><div>The PEA immunoassay was utilized to quantify serum concentrations of ninety-two inflammation-associated proteins among individuals with initial-onset LN (diagnosed concurrently with systemic lupus erythematosus (SLE), <em>n</em> = 23), patients with initial-onset non-LN manifestations (limited to cutaneous and musculoskeletal symptoms, specifically lupus arthritis (LA), <em>n</em> = 21), and age-matched healthy controls (HC, <em>n</em> = 22). Simultaneously, baseline clinical data were collected from the study population. Subsequently, machine-learning-based statistical modeling was employed to uncover prospective biomarkers indicative of initial-onset LN.</div></div><div><h3>Results</h3><div>A sum of 36 serum proteins was found to be differentially expressed in initial-onset LN relative to HC, comprising 25 upregulated and 11 downregulated proteins. Notably, transforming growth factor beta-1 proprotein, C-X-C motif chemokine 5, interleukin-15 receptor subunit alpha (IL-15RA), and C-X-C motif chemokine 11 were included in the final predictive model, achieving a sensitivity of 91.67 % and a specificity of 95.24 %. Compared with LA patients, 12 proteins were differentially regulated in the LN group, including 11 downregulated and 1 upregulated protein. Among these, Oncostatin-M, C<img>C motif chemokine 28, Fibroblast growth factor 19, IL-15RA, leukemia inhibitory factor, neurotrophin-3, and TNF-like weak inducer of apoptosis were incorporated into a model yielding a sensitivity of 74.07 % and specificity of 82.35 %.</div></div><div><h3>Conclusion</h3><div>The application of highly sensitive PEA profiling facilitated the identification of distinct serum protein signatures across SLE, initial-onset LN, and LA, uncovering multiple novel protein candidates. These promising biomarkers, whose precise role and predictive potential within the context of SLE merit further validation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157065"},"PeriodicalIF":3.7,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145428863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-01DOI: 10.1016/j.cyto.2025.157060
Yanshan Liu , Tuo Xu , Yeting Zhang , Mali Fang
Aims
Explore the expression of miR-503-5p in sepsis and its influence on the inflammatory response.
Methods
A total of 120 patients with sepsis were retrospectively selected as the research subjects, and 80 healthy individuals were simultaneously selected as the control group. Reverse transcription quantitative polymerase chain reaction was used to detect the expression of miR-503-5p and related genes. Pearson correlation analysis was used to determine the relationships between variables, and multivariate logistic regression analysis was applied to analyze the risk factors associated with sepsis. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of serum miR-503-5p levels for sepsis. Sepsis-model cells were created in vitro for the purpose of exploring the possible action mechanism of miR-503-5p in the context of sepsis.
Results
The expression of miR-503-5p in the serum of patients with sepsis is significantly upregulated, and it is positively correlated with the severity of the patients' condition and inflammatory indexes. miR-503-5p has a good diagnostic potential in sepsis. Furthermore, miR-503-5p exhibited a notable increase in expression within lipopolysaccharide (LPS)-stimulated THP-1 cells, which facilitated the inflammatory process. Mechanistically, miR-503-5p exacerbates the inflammatory response in sepsis via targeted suppression of peroxisome proliferator-activated receptor alpha (PPARA).
Conclusions
During sepsis, miR-503-5p shows elevated expression, and it facilitates the inflammatory response through the targeted suppression of PPARA.
{"title":"Clinical value and pro-inflammatory mechanism of miR-503-5p as a novel diagnostic biomarker for Sepsis","authors":"Yanshan Liu , Tuo Xu , Yeting Zhang , Mali Fang","doi":"10.1016/j.cyto.2025.157060","DOIUrl":"10.1016/j.cyto.2025.157060","url":null,"abstract":"<div><h3>Aims</h3><div>Explore the expression of miR-503-5p in sepsis and its influence on the inflammatory response.</div></div><div><h3>Methods</h3><div>A total of 120 patients with sepsis were retrospectively selected as the research subjects, and 80 healthy individuals were simultaneously selected as the control group. Reverse transcription quantitative polymerase chain reaction was used to detect the expression of miR-503-5p and related genes. Pearson correlation analysis was used to determine the relationships between variables, and multivariate logistic regression analysis was applied to analyze the risk factors associated with sepsis. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of serum miR-503-5p levels for sepsis. Sepsis-model cells were created in vitro for the purpose of exploring the possible action mechanism of miR-503-5p in the context of sepsis.</div></div><div><h3>Results</h3><div>The expression of miR-503-5p in the serum of patients with sepsis is significantly upregulated, and it is positively correlated with the severity of the patients' condition and inflammatory indexes. miR-503-5p has a good diagnostic potential in sepsis. Furthermore, miR-503-5p exhibited a notable increase in expression within lipopolysaccharide (LPS)-stimulated THP-1 cells, which facilitated the inflammatory process. Mechanistically, miR-503-5p exacerbates the inflammatory response in sepsis via targeted suppression of peroxisome proliferator-activated receptor alpha (PPARA).</div></div><div><h3>Conclusions</h3><div>During sepsis, miR-503-5p shows elevated expression, and it facilitates the inflammatory response through the targeted suppression of PPARA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157060"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145413024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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