Cytokine最新文献

{"title":"A systematic review and meta-analysis of the association between endothelial nitric oxide synthase (eNOS) rs2070744 polymorphism and preeclampsia","authors":"Md. Shafiul Hossen ,&nbsp;Md. Abdul Aziz ,&nbsp;Md Abdul Barek ,&nbsp;Mohammad Safiqul Islam","doi":"10.1016/j.cyto.2025.156870","DOIUrl":"10.1016/j.cyto.2025.156870","url":null,"abstract":"<div><h3>Objective</h3><div>Preeclampsia, characterized by hypertension and proteinuria, is a medical condition associated with maternal and fetal morbidity and mortality. Previous studies reported conflicting correlations between the <em>eNOS</em> rs2070744 variant and the occurrence of preeclampsia. Due to inconsistencies in findings, the purpose of the present meta-analysis was to explore the precise link between the <em>eNOS</em> rs2070744 variant and the development of preeclampsia.</div></div><div><h3>Methods</h3><div>The articles were retrieved from various online sources, including Cochrane Library, Google Scholar, EMBASE, PubMed, and Web of Science databases up to February 2024. Data were analyzed by Review Manager (RevMan) 5.4. We adhered to the PRISMA 2020 guidelines to conduct this meta-analysis.</div></div><div><h3>Results</h3><div>A total of 26 articles containing 3741 cases and 4920 controls were included for qualitative and quantitative data synthesis. In the overall population, we found a strong correlation between the <em>eNOS</em> rs2070744 variant and higher preeclampsia risk in recessive (CC vs. CT + TT: OR = 1.31, <em>p</em> = 0.017) dominant (CC + CT vs. TT: OR = 1.14, <em>p</em> = 0.051), co-dominant 2 (CC vs. TT: OR = 1.37, <em>p</em> = 0.011) and allelic (C vs. T: OR = 1.14, <em>p</em> = 0.022) models. Our study also explored similar outcomes among the Caucasian population in dominant (CC + CT vs. TT: OR = 1.16, <em>p</em> = 0.048), recessive (CC vs. CT + TT: OR = 1.46, <em>p</em> = 0.027), allele (C vs. T: OR = 1.18, <em>p</em> = 0.044), co-dominant 2 (CC vs. TT: OR = 1.53, <em>p</em> = 0.027), and co-dominant 3 (CC vs. CT: OR = 1.46, <em>p</em> = 0.002) models. Besides, a significant risk of preeclampsia in the African population was observed in co-dominant 2 (CC vs. TT: OR = 2.11, <em>p</em> = 0.009), dominant (CC + CT vs. TT: OR = 1.58, <em>p</em> = 0.002) and allelic (C vs. T: OR = 1.45, <em>p</em> = 0.001) models. However, no association of this polymorphism with preeclampsia risk was reported in Asian and mixed populations.</div></div><div><h3>Conclusion</h3><div>This study suggests a significant correlation between <em>eNOS</em> rs2070744 polymorphism and preeclampsia. However, more research on various ethnic groups is necessary to confirm the association.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156870"},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073044","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":"Effect of Saccharomyces cerevisiae β-glucan on the T helper cytokine profile","authors":"Patricia Vuscan ,&nbsp;Rutger J. Röring ,&nbsp;Brenda Kischkel ,&nbsp;Maria Tintoré ,&nbsp;Jordi Cuñé ,&nbsp;Carlos de Lecea ,&nbsp;Leo A.B. Joosten ,&nbsp;Mihai G. Netea","doi":"10.1016/j.cyto.2025.156871","DOIUrl":"10.1016/j.cyto.2025.156871","url":null,"abstract":"<div><div>ABBi16 is a high-complexity blend of β-1,3/1,6-glucans from <em>Saccharomyces cerevisiae</em> with strong immunomodulatory activities, that have been recently shown to support anti-tumoral immune responses through the induction of trained immunity. Whether ABBi16 also modulates the balance between the various T helper (Th) lymphocyte responses is not known. Here, we show that ABBi16 induces Th1 responses, as indicated by stimulation of IFNγ and TNF production by human peripheral blood mononuclear cells (PBMCs). Moreover, the elevated secretion of IL-10 and IL-22 suggests a potential regulatory response of the Th1/Th2/Th17 balance. Co-stimulating PBMCs with ABBi16 alongside Bacille Calmette-Guerin (BCG), IL-1beta + IL-23, and IL-12 + IL-18 cytokine combinations further enhanced Th1 polarization and IL-22 induction, hinting at an additive effect of β-glucan on both Th1 and regulatory Th17 immune responses. ABBi16 did not induce IL-17 production, the prototype pro-inflammatory product of Th17 responses, suggesting that it can be safely used as an oral supplement in patients with autoimmune conditions. These results highlight the potential of ABBi16 to regulate the Th1/Th2/Th17 balance toward antimicrobial and regulatory effects.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156871"},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint inhibitors mediate myocarditis by promoting macrophage polarization via cGAS/STING pathway","authors":"Zhenzhu Cao ,&nbsp;Yu Zhang ,&nbsp;Huihui Jia ,&nbsp;Xuan Sun ,&nbsp;Yuting Feng ,&nbsp;Han Wu ,&nbsp;Biao Xu ,&nbsp;Zhonghai Wei","doi":"10.1016/j.cyto.2025.156873","DOIUrl":"10.1016/j.cyto.2025.156873","url":null,"abstract":"<div><h3>Background</h3><div><strong>Immune checkpoint inhibitors</strong> has opened up new avenues for cancer treatment, but serious cardiac injury has emerged in their use. A large number of data have shown that abnormal activation of cytosolic DNA-sensing cyclic GMP-AMP synthase-interferon gene activator pathway is closely related to cardiovascular inflammation and autoimmune diseases. However, the pathophysiological function of the cGAS-STING cascade in myocarditis induced by <strong>Immune checkpoint inhibitors</strong> is unclear.</div></div><div><h3>Methods</h3><div>In order to establish a <strong>Immune checkpoint inhibitors</strong>-associated myocarditis model, BALB/c mice were injected with mouse cardiac troponin I peptide and anti-mouse programmed death 1 antibody. Echocardiography and HE staining were then performed to assess cardiac function and inflammation. Macrophages and damaged DNA in mouse heart tissue were detected by immunofluorescence. The mitochondrial damage of macrophages was observed by electron microscope. In vitro experiments, RAW264.7 was used to detect macrophage polarization after anti-PD-1 antibody induction and STING inhibition by qPCR and flow cytometry. Mitochondrial damage was detected by immunofluorescence, and activation of the cGAS-STING signaling pathway was evaluated by protein imprinting analysis.</div></div><div><h3>Results:</h3><div>In the Immune checkpoint inhibitors-associated myocarditis model, DNA damage was found to activate the cGAS-STING pathway and macrophages were polarized to M1 type. In vitro experiments, anti-PD-1 antibody activate the cGAS-STING pathway through the release of damaged DNA from macrophage mitochondrial damage, causing macrophage polarization into a pro-inflammatory phenotype leading to autoimmune myocarditis.</div></div><div><h3>Conclusion</h3><div>Our results suggested that the cGAS-STING pathway played a key role in myocarditis caused by immune checkpoint inhibitors. It provided a new possibility for Immune checkpoint inhibitors to be widely used in clinic.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156873"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062680","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":"Effects of Fisetin and Nicorandil on adjuvant-induced rheumatoid arthritis in rats: Emerging role of TLR4/NF-κB-induced Pyroptosis, Nrf-2/HO-1, and OPG/RANKL pathways","authors":"Asmaa H. Okasha ,&nbsp;Islam Ibrahim Hegab ,&nbsp;Monira A. Seleem ,&nbsp;Asmaa R. Azzam ,&nbsp;Sarah Ibrahim ,&nbsp;Asmaa A. Ghalwash ,&nbsp;Rehab M. El-Gohary","doi":"10.1016/j.cyto.2025.156876","DOIUrl":"10.1016/j.cyto.2025.156876","url":null,"abstract":"<div><h3>Aim and <strong>background</strong></h3><div>Our study explored the novel mechanisms implicated in the anti-rheumatic potential of fisetin and/or nicorandil (NIC) intervention.</div></div><div><h3>Methods and Materials:</h3><div>Fifty male rats were categorized into; control, rheumatoid arthritis (RA), fisetin-treated RA, NIC-treated RA, and co-treated RA groups. We assessed paw thickness, arthritis indices, serum CRP, RF, OPG, RANKL, and gene expressions of synovial TLR4, NLRP3, caspase-1, GSDMD, Nrf-2, and HO, along with synovial histopathology and NF-κB immunoreactivity.</div></div><div><h3>Results</h3><div>The combined therapy demonstrated significantly better anti-rheumatic potential, suppressing oxidative stress and NF-κB, downregulating synovial TLR4, NLRP3, caspase-1, GSDMD, and increasing serum OPG while decreasing RANKL, confirmed by histopathological findings.</div></div><div><h3>Conclusion</h3><div>Our investigation uncovered the TLR4/NF-κB pyroptotic signaling, Nrf-2/HO-1, and OPG/RANKL pathways as novel mechanistic insights into the anti-rheumatoid potential of fisetin and/or NIC, with superiority of combination approach, providing a beacon of hope for RA patients in terms of optimizing treatment protocol effectiveness and patient outcomes.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156876"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062677","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":"Immune mechanisms in multiple sclerosis: CD3 levels on CD28+ CD4+ T cells link antibody responses to human herpesvirus 6","authors":"Liang Cao ,&nbsp;Chen Chen ,&nbsp;Wenjun Pi ,&nbsp;Yi Zhang ,&nbsp;Sara Xue ,&nbsp;Voon Wee Yong ,&nbsp;Mengzhou Xue","doi":"10.1016/j.cyto.2025.156866","DOIUrl":"10.1016/j.cyto.2025.156866","url":null,"abstract":"<div><div>Compelling evidence suggests a significant association between antibody-mediated immune responses and multiple sclerosis (MS). However, the exact causal relationships between these immune responses and MS remain unclear. In this study, we conducted a comprehensive examination of the link between antibody-mediated immune responses and MS via Mendelian randomization (MR) analysis to identify specific infectious pathogens potentially involved in the onset and progression of MS. We compared immune cell infiltration between MS patients and control subjects. Furthermore, single-cell sequencing was employed to conduct a comparative analysis of the marker genes associated with each cell subtype between individuals diagnosed with MS and the control cohort. We revealed connections between antibody-mediated immune responses and immune cells, as well as the associations between these immune cells and MS. We discovered that CD3 levels on CD28⁺ CD4⁺ T cells significantly influence MS progression by altering the ratio of human herpesvirus 6 (HHV-6). These findings provide novel insights into the biological mechanisms underlying HHV–6–mediated MS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156866"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062681","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":"Transforming growth factor beta induces interleukin-11 expression in osteoarthritis","authors":"Juliane Lokau ,&nbsp;Miriam Bollmann ,&nbsp;Yvonne Garbers ,&nbsp;Eugen Feist ,&nbsp;Christoph H. Lohmann ,&nbsp;Jessica Bertrand ,&nbsp;Christoph Garbers","doi":"10.1016/j.cyto.2025.156863","DOIUrl":"10.1016/j.cyto.2025.156863","url":null,"abstract":"<div><div>Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and possesses both pro- and anti-inflammatory properties. IL-11 activates its target cells via binding to a membrane-bound IL-11R and subsequent formation of a homodimer of the signal-transducing receptor gp130. Thus, the expression pattern of the IL-11R determines which cells can be activated by IL-11. However, knowledge about IL-11 target cells and cells that secrete IL-11 are sparse, and the overall roles of IL-11 in inflammatory diseases are largely unexplored. In this study, we show that high amounts of IL-11 can be detected via ELISA in the synovial fluid of osteoarthritis (OA) patients in comparison to rheumatoid arthritis (RA) patients. Using primary cells and tissue of OA patients, we show that IL-11 is expressed by chondrocytes in cartilage, but not in the synovium. We further identify the cytokine transforming growth factor β 1(TGF-β1) as a potent inducer of IL-11 secretion in both primary chondrocytes and fibroblasts, and TGF-β1 and IL-11 levels correlate significantly in the synovial fluid of OA patients. Using immunohistochemistry, we show that both cartilage and synovium express IL-11R, and the amount of IL-11R is independent of the disease severity. Primary chondrocytes and fibroblasts from OA patients respond to IL-11 stimulation with potent activation of the Jak/STAT3 signaling cascade, suggesting that these cell types are not only the source, but also the targets of IL-11 in OA patients. Our results uncover IL-11 as a potential new target for therapy in OA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156863"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR3 as an emerging molecule facilitating pyroptosis in the context of rheumatoid arthritis: A study combined bioinformatics and experimental validation","authors":"Meng-yuan Zhou ,&nbsp;Hong-yan Feng ,&nbsp;Tian-tian Wang ,&nbsp;Ze-shan Xu ,&nbsp;Sheng-long Gu ,&nbsp;Ling-ling Li ,&nbsp;Li Cai ,&nbsp;Rong Li","doi":"10.1016/j.cyto.2025.156875","DOIUrl":"10.1016/j.cyto.2025.156875","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is an inflammatory disease of the joints mediated by immune cells. As an immune-related mode of cell death, pyroptosis has yet to be fully understood in RA. This research identified novel pyroptosis-related markers in RA and confirmed its functional significance in RA.</div></div><div><h3>Methods</h3><div>Initially, crucial pyroptosis-related genes of RA were identified through GEO database, and biological pathways were determined through enrichment analysis. Then, PPI network, WGCNA and CIBERSORT analysis was utilized to screen hub genes and evaluate immune cell infiltration levels. Finally, validation experiments determined hub genes expression and regulatory roles in RA pathogenesis, and screened potential therapeutic drugs.</div></div><div><h3>Results</h3><div>A total of 46 DEPRGs in RA were identified, which involved in NOD-like receptor and Toll-like receptor signaling pathway. Further screening revealed 3 crucial hub genes: CCL5, LY96, and TLR3 had significantly increased expression in RA synovial tissue and FLS, which might become diagnostic markers of RA. Analysis of immune infiltration revealed that hub genes exhibited associations with plasma cells, T lymphocytes, and macrophages. Further study on the crucial hub gene TLR3 revealed that knocking down TLR3 significantly inhibited the RA FLS hyperproliferation and pyroptosis, and dexamethasone and doxorubicin, as potential drugs, could treat RA by inhibiting TLR3.</div></div><div><h3>Conclusion</h3><div>Our study indicates that high expression of TLR3 promotes FLS pyroptosis and RA progression, suggesting its potential as both a biomarker and a therapeutic target for RA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156875"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062733","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":"Knockout or treatment with an antagonist of formyl peptide receptor 1 protects mice from sepsis by inhibiting inflammation","authors":"Gang Ma ,&nbsp;Jie Ma ,&nbsp;Baofu Qu ,&nbsp;Caixia Zhang ,&nbsp;Jinyuan Zhu ,&nbsp;Yi Chen ,&nbsp;Yujie Ma ,&nbsp;Xiangkun Meng","doi":"10.1016/j.cyto.2025.156872","DOIUrl":"10.1016/j.cyto.2025.156872","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is an infection-related systemic inflammation with high mortality rates. Activation of formyl peptide receptor 1 (FPR1) in immune cells can promote their chemotaxis and inflammatory response, which imbalances immune response during the process of sepsis. FPR1 blockade did diminish systemic inflammatory response during bacterial infection. Accordingly, this study tested the hypothesis that knockout or treatment with an antagonist of FPR1 could protect animals from sepsis-related death.</div></div><div><h3>Methods</h3><div>Wild-type (WT) or <em>Fpr1</em> gene knockout (<em>Fpr1</em>^−/−) C57BL/6 mice were subjected to the process of cecal ligation and puncture (CLP) to induce different grades of sepsis. Some WT mice were treated with cinnamoylphenylalanine-(D)leucine-phenylalanine-(D)leucine-phenylalanine (cFLFLF), a FPR1 antagonist. Their survival rate was evaluated, their blood and peritoneal flushing samples were collected at 6 and 24 h after the induction of sepsis for biochemical analyses. We also enrolled 143 sepsis patients, their blood and neutrophil samples were collected for analysis of FPR1 expression by RT-qPCR, and their 28-day survival was recorded.</div></div><div><h3>Results</h3><div>All mice died by day 6 after high grade sepsis regardless of <em>Fpr1</em>^−/− or cFLFLF treatment. <em>Fpr1</em> gene knockout or cFLFLF treatment increased the survival rate of mice with a mid-to-low grade of sepsis, accompanied by a significant decrease in the levels of serum and peritoneal inflammatory markers (IL-6, IL-1β and TNF-α). Induction of sepsis increased the percentages of blood neutrophils, and the counts of peritoneal bacterial colony forming units, but decreased body temperature in WT mice, but not in the <em>Fpr1</em>^−/− mice or cFLFLF-treated sepstic mice. Analysis of clinical data indicated that sequential organ failure assessment score and old age were independent risk factors for 28-day mortality.</div></div><div><h3>Conclusion</h3><div><em>Fpr1</em> gene knockout or cFLFLF treatment increased the survival rate of animals with a mid-to-low grade of sepsis, in part by inhibiting abdominal and systemic inflammation during the early period of sepsis. FPR1 protein level in neutrophils was not an independent risk factor of 28-day mortality in sepsis patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156872"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062685","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":"Prognostic significance of cytokine dysregulation in critically ill COVID-19 patients","authors":"Fabian Fellipe Bueno Lemos ,&nbsp;Luana Weber Lopes ,&nbsp;Gabriel Carvalho Brito ,&nbsp;Airton Idalecio Sousa Viana ,&nbsp;Caroline Tianeze de Castro ,&nbsp;Marcel Silva Luz ,&nbsp;André Pereira Gonçalves ,&nbsp;Rafael Santos Dantas Miranda Dórea ,&nbsp;Filipe Antônio França da Silva ,&nbsp;Breno Bittencourt de Brito ,&nbsp;Maria Luísa Cordeiro Santos ,&nbsp;Geovani Moreno Santos Júnior ,&nbsp;Maria Teresa Araújo de Lorenzo Barcia ,&nbsp;Renata de Amorim Marques ,&nbsp;André Bezerra Botelho ,&nbsp;Anna Carolina Saúde Dantas ,&nbsp;Fillipe Dantas Pinheiro ,&nbsp;Adriano Fernandes Teixeira ,&nbsp;Cláudio Lima Souza ,&nbsp;Márcio Vasconcelos Oliveira ,&nbsp;Fabrício Freire de Melo","doi":"10.1016/j.cyto.2025.156867","DOIUrl":"10.1016/j.cyto.2025.156867","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes—particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU).</div></div><div><h3>Methods</h3><div>We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation.</div></div><div><h3>Results</h3><div>Deceased patients exhibited significantly higher levels of interleukin (IL)-1β, IL-2, IL-6, transforming growth factor (TGF)-β, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1β and TGF-β had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity.</div></div><div><h3>Conclusion</h3><div>Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156867"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057643","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":"TGF-beta plays dual roles in immunity and pathogenesis in leishmaniasis","authors":"Susmita Barik ,&nbsp;Sanghamitra Goswami ,&nbsp;Prakash Kumar Nanda ,&nbsp;Argajit Sarkar ,&nbsp;Bhaskar Saha ,&nbsp;Arup Sarkar ,&nbsp;Surajit Bhattacharjee","doi":"10.1016/j.cyto.2025.156865","DOIUrl":"10.1016/j.cyto.2025.156865","url":null,"abstract":"<div><div>Transforming growth factor-beta (TGF-β), displaying a dual role in immunosuppression and pathogenesis, has emerged as a key regulator of anti-leishmanial immune responses. In <em>Leishmania</em> infections, TGF-β drives immune deviation by enhancing regulatory T-cell (T-reg) differentiation and inhibiting macrophage activation, suppressing critical antiparasitic responses. This cytokine simultaneously promotes fibroblast proliferation, extracellular matrix production, and fibrosis in infected tissues, which aids in wound healing but impedes immune cell infiltration, particularly in visceral leishmaniasis, where splenic disorganization and compromised immune access are notable. In conjunction with IL-6, TGF-β modulates pathogenic Th17 responses which intensify inflammatory damage and disrupt tissue architecture. While TGF-β's immunosuppressive actions enable parasite persistence, its role in maintaining tissue integrity introduces therapeutic potential. Targeted modulation of TGF-β signaling, through selective inhibitors of TGF-β receptors or signaling intermediates, has the potential to enhance parasite clearance while minimizing immunopathology. Experimental studies suggest that phase-specific intervention strategies may allow for controlled immunostimulation or fibrosis reduction, enhancing host resistance without incurring inflammatory injury. This review discusses the intricate role of TGF-β in orchestrating immune deviation, fibrosis, and pathogenesis in leishmaniasis, proposing novel therapeutic avenues for selective modulation of TGF-β pathways to restore host immunity.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156865"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057644","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}