Cytokine最新文献

{"title":"Serum IL-6 levels correlate with surgical stress factors in newborns with congenital diaphragmatic hernia","authors":"Takao Kobayashi ,&nbsp;Sota Iwatani ,&nbsp;Toshihiko Ikuta,&nbsp;Seiji Yoshimoto","doi":"10.1016/j.cyto.2025.157053","DOIUrl":"10.1016/j.cyto.2025.157053","url":null,"abstract":"<div><h3>Background</h3><div>Peri-operative management in congenital diaphragmatic hernia (CDH) remains a significant challenge associated with mortality and morbidity. Although interleukin-6 (IL-6) reflects surgical stress in adults, its peri-operative dynamics in newborns remain unclear. This study investigated changes in IL-6 levels in CDH newborns and their association with surgical stress factors and post-operative complications.</div></div><div><h3>Methods</h3><div>In this single-center study, CDH newborns who underwent surgical repair between 2010 and 2022 were retrospectively studied. Changes in serum IL-6 and C-reactive protein (CRP) levels from 72-h pre-operatively to 96-h post-operatively were assessed. Correlations between peak peri-operative IL-6/CRP levels and surgical stress-related factors or early post-operative complications were also explored in this preliminary analysis.</div></div><div><h3>Results</h3><div>Of 49 newborns, 20 had available data to evaluate peri-operative IL-6 and CRP levels. Serum IL-6 peaked [median: 122.7 (62–1898) pg/mL] at 10-h (1–42) postoperatively, while CRP peaked [median: 2.40 (0.24–8.31) mg/dL] at 38-h (12–47). Peak IL-6 levels correlated negatively with postnatal time (<em>r</em>_<em>s</em> = −0.610) and positively with intra-operative blood loss and 24-h post-operative transfusion volumes (<em>r</em>_<em>s</em> = 0.497 and 0.510).</div></div><div><h3>Conclusions</h3><div>In CDH newborns, serum IL-6 levels increase during the 24–48-h post-operative period and return to baseline by the 48–72-h period. Although this is a preliminary study with a limited sample size, assessing peak IL-6 levels may provide a useful indicator of surgical stress and help optimize peri-operative management, including transfusion strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157053"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145306491","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}

{"title":"Serum interleukin-1 receptor antagonist levels are a useful marker of disease activity and risk of relapse in large vessel vasculitis.","authors":"Koji Suzuki ,&nbsp;Sho Ishigaki ,&nbsp;Mitsuhiro Akiyama ,&nbsp;Keiko Yoshimoto ,&nbsp;Waleed Alshehri ,&nbsp;Kanako Shimanuki ,&nbsp;Koichi Saito ,&nbsp;Hiroshi Takei ,&nbsp;Noriyasu Seki ,&nbsp;Hideto Tsujimoto ,&nbsp;Kenji Chiba ,&nbsp;Yuko Kaneko","doi":"10.1016/j.cyto.2025.157059","DOIUrl":"10.1016/j.cyto.2025.157059","url":null,"abstract":"<div><h3>Objective</h3><div>To examine whether serum interleukin-1β (IL-1β) or IL-1 receptor antagonist (IL-1Ra) levels are associated with disease activity or relapse risk in large vessel vasculitis (LVV), including giant cell arteritis (GCA) and Takayasu arteritis (TAK).</div></div><div><h3>Methods</h3><div>Twenty one patients with treatment-naive, active LVV (13 with GCA and 8 with TAK), and 14 healthy individuals were enrolled in the study. Serum levels of IL-1β, IL-1Ra, IL-2, IL-6, IL-12p40, IL-17, IL-23, IFN-γ, and TNF-α were measured. Association with C-reactive protein (CRP) levels, Indian Takayasu clinical activity score (ITAS-A), and relapse were analyzed.</div></div><div><h3>Results</h3><div>IL-1Ra levels were significantly higher in patients with with TAK (465.3 pg/mL) and GCA (384.9 pg/mL) compared to healthy individuals (170.4 pg/mL; <em>p</em> &lt; 0.001). IL-6 levels were also elevated in LVV, while IL-1β and IFN-γ were increased only in GCA and IL-17 levels were increased only in TAK. IL-1Ra levels positively correlated with ITAS-A scores in TAK and with CRP levels in GCA. IL-6 correlated with CRP in both diseases; IL-1β and other cytokines showed no such association. During follow-up, six patients (five with GCA and one with TAK) experienced symptomatic relapse. In GCA, baseline IL-1Ra levels were significantly lower in those who relapsed compared to non-relapsed patients (270.8 vs. 616.4 pg/mL; <em>p</em> = 0.008). No significant difference in other cytokine levels were observed. Receiver operating characteristic analysis demonstrated that IL-1Ra levels &gt;340.4 pg/mL could distinguish non-relapsed from relapsed cases (AUC = 0.95).</div></div><div><h3>Conclusion</h3><div>Serum IL-1Ra levels correlate with CRP levels in GCA and ITAS-A scores in TAK and serve as a predictive biomarker for relapse.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157059"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317970","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}

{"title":"Cardiotrophin-1 as a predictor of critical COVID-19, mortality, and persistence of pulmonary fibrosis after the acute phase of infection","authors":"María Íñiguez ,&nbsp;Patricia Pérez-Matute ,&nbsp;Pablo Villoslada-Blanco ,&nbsp;Emma Recio-Fernandez ,&nbsp;Diana Ezquerro-Pérez ,&nbsp;Jorge Alba ,&nbsp;Concepción García-García ,&nbsp;Galadriel Pellejero ,&nbsp;M. Lourdes Ferreira-Laso ,&nbsp;Dolores del Puerto García ,&nbsp;Carlos Ruiz-Martínez ,&nbsp;José A. Oteo","doi":"10.1016/j.cyto.2025.157037","DOIUrl":"10.1016/j.cyto.2025.157037","url":null,"abstract":"<div><div>Pulmonary fibrosis remains a long-term complication in some COVID-19 recovered patients, particularly in those who suffered from severe disease. Cardiotrophin-1 (CT-1) is an antiapoptotic cytokine related with the progression of fibrotic disease in heart and kidney. This study examines the association between CT-1 plasma levels, COVID-19 severity, and post-COVID pulmonary fibrosis. CT-1 levels were analyzed in patients with asymptomatic/mild (<em>n</em> = 33), severe (<em>n</em> = 39), and critical (<em>n</em> = 57) COVID-19, as well as in those with post-COVID pulmonary fibrosis. Elevated CT-1 levels were associated with a higher risk of severe disease, mortality, and persistent pulmonary fibrosis even a year after discharge. Furthermore, CT-1 was associated with non-COVID-19-related pulmonary fibrosis, suggesting a broader role of this cytokine in chronic lung diseases. These findings propose CT-1 as a potential biomarker and therapeutic target for pulmonary fibrosis and provide new insights for its role in chronic respiratory conditions, such as idiopathic pulmonary fibrosis (IPF), post-COVID interstitial lung disease or chronic hypersensitivity pneumonitis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157037"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156263","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}

{"title":"Inhibiting TGF-β signaling pathway for disease therapy: challenges and opportunities","authors":"XiaoYan Gao ,&nbsp;XiuDan Li ,&nbsp;CongYing Zhang ,&nbsp;Jing Zhou ,&nbsp;Kai Gu ,&nbsp;XiaoQiang Liu ,&nbsp;ChunYing Bai","doi":"10.1016/j.cyto.2025.157048","DOIUrl":"10.1016/j.cyto.2025.157048","url":null,"abstract":"<div><div>Transforming growth factor (TGF)-β is a multifunctional cytokine expressed in nearly all human tissues and cell types. The TGF-β signaling pathway is essential for embryonic development, cell and tissue differentiation, and tissue homeostasis in adults. Aberrant regulation of this pathway is closely associated with various diseases, indicating that the TGF-β signaling pathway represents a promising target for therapeutic intervention. Notably, diseases linked to the disruption of the TGF-β signaling pathway include cancer, vascular disorders, wound healing complications, tissue fibrosis, and autoimmune diseases. The development and optimization of selective inhibitors targeting TGF-β could provide viable therapeutic options for the clinical treatment of these conditions. Consequently, targeting the cytokine TGF-β and its signaling pathway may offer a novel and promising treatment strategy for related diseases. This review summarizes recent studies on the role of TGF-β in the pathogenesis and treatment of associated diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157048"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218246","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}

{"title":"PAX9 and Col1A1 may regulate the progression of colon cancer through interactions with the TGF-β1/Smad pathway","authors":"Chao huang,&nbsp;Bingjun Liang,&nbsp;Weizeng Shen","doi":"10.1016/j.cyto.2025.157051","DOIUrl":"10.1016/j.cyto.2025.157051","url":null,"abstract":"<div><h3>Objective</h3><div>Transforming growth factor-β1 (TGF-β1) is widely involved in the progression of advanced cancer through the downstream Smad pathway, but the underlying mechanisms are still not fully understood. This project aimed to explore the relationship between key molecules of the TGF-β1/Smad pathway and the progression of colon cancer, as well as its upstream and downstream regulatory mechanisms.</div></div><div><h3>Methods</h3><div>Clinical data and related gene expression data of patients with colon cancer were retrieved from clinical databases and genomic libraries such as TCGA-COAD, GEO, and ENCODE. The expression levels of key molecules of the TGF-β1/Smad pathway (TGF-β1, TGF-β1 receptor, and SMAD2/3/4) in colon cancer/paracancerous tissue samples and their relationships with prognosis were analyzed. R packages and RStudio were used to analyze genes that were differentially expressed between colon cancer and normal tissues and the promoter regions bound by Smad2/3. JASPAR and GO/KEGG enrichment were used to predict upstream transcription factors and downstream regulatory genes of the TGF-β1/Smad pathway.</div></div><div><h3>Results</h3><div>A total of 459 patients with colon cancer were included in this study. Different TGF-β1 expression levels significantly affected the overall survival (OS) and disease-free survival (DFS) of patients with colon cancer (<em>P</em> &lt; 0.05). The expression of TGF-β1/Smad pathway molecules was significantly associated with the specific stage of cancer. A total of 954 genes had Smad2/3 binding sites in their promoter regions. The expression of the main transcription factor, paired box 9 (PAX9), that regulates the Smad2/3 pathway was generally higher in colon cancer tissues than in normal tissues. The expression of the transcription factor vitamin D (1,25- dihydroxyvitamin D3) receptor (VDR) was significantly different among different cancer types, especially in colon cancer, where its expression was significantly higher than that in normal tissues. Col1A1 expression was strongly correlated with that of TGF-β1 (<em>R</em> = 0.79, <em>P</em> &lt; 0.001). High expression of COL1A1 tended to reduce overall survival (<em>P</em> = 0.072), and the high-expression group had a 1.6 times lower risk of DFS than the low-expression group did (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>The TGF-β1/Smad pathway may regulate the progression and prognosis of colon cancer in conjunction with multiple upstream and downstream target genes (including PAX9, VDR, and Col1A1) and is related to cancer stage.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157051"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297852","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}

{"title":"Association of the soluble form of the endothelial Tie2 receptor with organ failure and mortality in patients with sepsis and ARDS","authors":"Nicolas J. Wegmann ,&nbsp;Dorothea M. Heuberger ,&nbsp;Gabor Kadler ,&nbsp;Benjamin Seeliger ,&nbsp;Thorben Pape ,&nbsp;Klaus Stahl ,&nbsp;Mattia M. Müller ,&nbsp;Sascha David","doi":"10.1016/j.cyto.2025.157062","DOIUrl":"10.1016/j.cyto.2025.157062","url":null,"abstract":"<div><h3>Introduction</h3><div>Tie2 is an endothelial surface receptor critically involved in angiogenesis, cell-integrity, and survival. During inflammatory disorders such as sepsis and ARDS, the receptor is shed from the endothelial surface, contributing to a reduction of its protective downstream signaling ultimately contributing to endothelial permeability and thereby capillary leakage. This study investigates the association of the soluble form of Tie2 (sTie2), with multiorgan failure, requirement of dialysis and mortality.</div></div><div><h3>Methodology</h3><div>We conducted a biomarker study using serum samples from sepsis and/or ARDS patients admitted to the medical intensive care unit (ICU) of Hannover Medical School. sTie2 was quantified by Multiplex Luminex Assay in serum samples collected on the day of ICU admission. Correlations between sTie2 levels and baseline SOFA-score, duration of vasopressor therapy, and duration of mechanical ventilation were evaluated using Pearson's correlation coefficient. The Wilcoxon rank-sum test was employed to compare sTie2 levels between individuals with and without renal replacement therapy, as well as between survivors and non-survivors. Cox regression models were applied to assess the independent association of sTie2 with 28-day mortality.</div></div><div><h3>Results</h3><div>sTie2 levels showed an inverse correlation with the SOFA-score (<em>R</em> = −0.2, <em>p</em> = 0.003) and were lower in patients requiring renal replacement therapy (17.4 [12.25–22.48] vs. 21.35 [14.91–29.08] ng/ml, p = 0.003) and in non-survivors (14.54 [10.96–15.02] vs. 21.01 [15–28.12] ng/ml, <em>p</em> &lt; 0.001). No correlation was found between sTie2 and the number of days requiring vasopressor therapy or mechanical ventilation. Using multivariable cox regression, sTie2 was independently associated with mortality at 28-days (sTie2, log(ng/ml) – HR 0.35, 95% CI 0.21–0.57, <em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>In this study of severely ill ICU patients, sTie2 was inversely related to severity of disease and to outcome. If the decrease in sTie2 is adaptive or maladaptive remains unclear but future investigations are required analysing the exact pathophysiological role of sTie2 to evaluate the biomarker as a potential target for the treatment of capillary leakage in patients with sepsis and/or ARDS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157062"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145375630","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}

{"title":"Interferon tau in ruminant reproduction: Mechanisms of maternal recognition of pregnancy and implications for fertility enhancement","authors":"Iqra Batool ,&nbsp;Rehana Kausar ,&nbsp;Muhammad Shahbaz Qamar","doi":"10.1016/j.cyto.2025.157035","DOIUrl":"10.1016/j.cyto.2025.157035","url":null,"abstract":"<div><div>Low conception rates and early embryonic loss remain major constraints to reproductive efficiency in ruminants, particularly during the peri-implantation period. Maternal recognition of pregnancy (MRP) is largely mediated by interferon tau (IFNT), a ruminant-specific type I interferon secreted by the elongating conceptus. Initially recognized for its anti-luteolytic action through suppression of endometrial prostaglandin F2α, (PGF2α). IFNT is now known to exert systemic effects beyond the uterus. It induces interferon-stimulated genes in endometrial and peripheral immune cells, shaping an immune environment conducive to embryo tolerance. By modulating nuclear factor kappa B, signal transducer and activator of transcription 1, and interferon regulatory factors, IFNT downregulates pro-inflammatory cytokines such as tumor necrosis factor alpha and interferon gamma, while enhancing anti-inflammatory mediators including interleukin-10 and interleukin-4. This shift promotes a T-helper 2-dominant immune profile favorable for maternal–fetal tolerance. In addition, IFNT safeguards corpus luteum function by mitigating PGF2α-induced luteolysis and preserving vascular integrity. This occurs through downregulation of pro-regression genes such as transforming growth factor beta 1, endothelin 1, thrombospondin 1/2, and serpin family E member 1, alongside upregulation of angiogenic mediators such as platelet-derived growth factor subunit B. These actions stabilize the luteal microenvironment and ensure sustained progesterone secretion. This review highlights IFNT's pivotal role in MRP, emphasizing its endocrine and paracrine actions on luteal maintenance, ISG induction, and immune modulation. It also explores IFNT's potential as a biomarker for early pregnancy detection and its applications in reproductive biotechnology, with bovine data supported by ovine, murine, and human models for translational insights.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157035"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102496","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}

{"title":"Neuregulin 4 attenuates osteoarthritis by decreasing macrophage M1 polarization through PI3K/AKT signaling","authors":"Chao Wang ,&nbsp;Jinjian Zheng ,&nbsp;Chengxin Li ,&nbsp;Puyi Sheng ,&nbsp;Linli Zheng","doi":"10.1016/j.cyto.2025.157036","DOIUrl":"10.1016/j.cyto.2025.157036","url":null,"abstract":"<div><div>Altered polarization of synovial macrophages has been identified as a key pathogenic factor in sustaining synovial inflammation and driving osteoarthritis(OA) progression.Neuregulin 4 (Nrg4) is widely involved in inflammatory diseases, such as hepatic inflammation, Crohn's disease, and atherosclerosis.In this study, we aimed to investigate the effects of Nrg4 on macrophages and synovitis and to elucidate the underlying mechanisms in the development of OA.We first evaluated the expression of Nrg4 and ErbB4 in OA patients and mouse model. The adeno-associated virus 5 vector carrying the Nrg4 gene (AAV5-Nrg4) was injected into the knee joints to overexpress Nrg4 in two OA models.In vitro, RAW264.7 macrophages and mouse bone marrow-derived macrophages (BMDMs) were cultured, induced to M1 macrophages, and then treated with Nrg4. RNA interference (RNAi) technique was used to inhibit the expression of the Nrg4 receptor ErbB4.The results demonstrated that Nrg4-ErbB4 signaling was decreased during OA. In vitro experiments showed that Nrg4 treatment significantly inhibited the M1 polarization of RAW264.7 cells and BMDMs and down-regulated the expression of pro-inflammatory genes.RNA sequencing (RNA-seq) analysis and related experiments revealed that Nrg4 regulated macrophage polarization mainly by inhibiting the PI3K/AKT signaling pathway.Intra-articular injection of AAV5-Nrg4 effectively alleviated joint damage and synovitis in collagenase-induced OA (CIOA) and destabilization of the medial meniscus(DMM)-induced OA models.</div><div>Nrg4-mediated suppression of M1 macrophage polarization in vivo was evidenced by attenuated iNOS concomitant with upregulated CD206 expression.In conclusion, our findings demonstrated that targeting Nrg4-ErbB4 axis may be a promising way to treat OA by reducing M1 macrophage polarization in synovial tissues.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157036"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102514","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}

{"title":"Rationalized combinatorial targeting of immune co-receptors leads to tumor regression","authors":"Saleha Nisar ,&nbsp;Prashant Chauhan ,&nbsp;Ashok Patidar ,&nbsp;Neelam Bodhale ,&nbsp;Uddipan Sarma ,&nbsp;Kalpana Pai ,&nbsp;Bhaskar Saha","doi":"10.1016/j.cyto.2025.157030","DOIUrl":"10.1016/j.cyto.2025.157030","url":null,"abstract":"<div><div>Different co-stimulatory and co-inhibitory molecules influence the dynamicity of an immune response. As their expression levels may collectively decide the amplitude and quality of an anti-tumor immune response, we proposed that the expression of these molecules would be dynamically modulated during a progressive tumor growth and that the study of their expression levels would guide fixing a combinatorial target for anti-tumor immunotherapy. Based on the kinetics of expression of 33 immune molecules within the tumor and draining lymph nodes during RM-1-induced progressive prostate tumor model in C57BL/6 mice, a three-phase combinatorial anti-tumor immunotherapy was designed. Phase- specific treatments with combinations of blocking antibodies against co-inhibitory receptors and agonistic antibodies against stimulatory receptors resulted in significant tumor regression and cytokines' expression, suggesting a strategic personalized anti-tumor immunotherapy with enhanced therapeutic efficacy, reduced toxicity and the risk of treatment failures.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157030"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079279","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}

{"title":"IL-33 links inflammation and bone remodeling in experimental spondyloarthritis and human joint biopsies","authors":"Susana Aideé González-Chávez ,&nbsp;Mario Loya-Rivera ,&nbsp;Soumya Nair ,&nbsp;Rodrigo Prieto-Carrasco ,&nbsp;Eduardo Chaparro-Barrera ,&nbsp;Daniel Alberto Ruizesparza-Hinojos ,&nbsp;Sourav Roy ,&nbsp;César Pacheco-Tena","doi":"10.1016/j.cyto.2025.157031","DOIUrl":"10.1016/j.cyto.2025.157031","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the pathogenic role of IL-33 in spondyloarthritis (SpA) by analyzing its expression in both murine and human joint tissues and functionally assessing its impact on fibroblasts. The study evaluated synovial and entheseal biopsies from patients with SpA to explore the potential contribution of IL-33 to joint inflammation and tissue remodeling.</div></div><div><h3>Methods</h3><div>A spontaneous arthritis model (SpAD) in DBA/1 mice was used to assess IL-33 expression via histology, immunohistochemistry, transcriptomics, RT-qPCR, and western blot. Sacroiliac and tarsal biopsies from patients with SpA were also analyzed. Differential gene expression was checked, and pathway enrichment was performed using Ingenuity Pathway Analysis. Primary fibroblasts were isolated from the joints of the mice's front and rear limbs, transfected with siRNA targeting <em>Il33</em>, and evaluated by RT-qPCR and western blot for inflammatory (<em>Tnf</em>, <em>Nfkb</em>) and osteogenic (<em>Wnt2</em>, <em>Bmp2</em>) markers. Cell viability was assessed via MTT assay.</div></div><div><h3>Results</h3><div>IL-33 expression was elevated in murine and human SpA joints, with strong cartilage and subchondral bone localization. Transcriptomic data indicated upregulation of IL-33 signaling and enrichment of proinflammatory and fibrotic pathways. Silencing of <em>Il33</em> in fibroblasts significantly reduced IL-33 protein levels and decreased <em>Tnf</em> and <em>Wnt2</em> expression at both mRNA and protein levels, while <em>Bmp2</em> reduction was observed only at the transcript level.</div></div><div><h3>Conclusion</h3><div>IL-33 contributes to joint inflammation and may regulate osteogenic pathways implicated in pathological bone formation. These findings support IL-33 as a potential dual-action therapeutic target in SpA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157031"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079308","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}