Cytokine最新文献

{"title":"Ontogeny of plasma cytokine and chemokine concentrations across the first four months of human life in a Papua new Guinean cohort","authors":"Athena N. Nguyen ,&nbsp;Thomas S. Kouyate ,&nbsp;Rebecca Ford ,&nbsp;Geraldine Masiria ,&nbsp;Joe Jude ,&nbsp;Alec L. Plotkin ,&nbsp;Oludare A. Odumade ,&nbsp;Joann Diray-Arce ,&nbsp;Olubukola T. Idoko ,&nbsp;Rym Ben-Othman ,&nbsp;on behalf of EPIC-HIPC consortium,&nbsp;Beate Kampmann ,&nbsp;Tobias R. Kollmann ,&nbsp;Peter Richmond ,&nbsp;Ofer Levy ,&nbsp;Anita H.J. van den Biggelaar ,&nbsp;William Pomat ,&nbsp;Kinga K. Smolen","doi":"10.1016/j.cyto.2025.157076","DOIUrl":"10.1016/j.cyto.2025.157076","url":null,"abstract":"<div><div>Dynamic molecular changes in early life follow a robust ontogeny as the infant immune system adapts to the demands of its new environment. Studies of plasma immunomodulatory cytokines and chemokines have previously demonstrated ontogenetic patterns of immune development across the first week of life. However, how plasma cytokine and chemokines concentrations evolve over the first 4 months of life remains unknown. In this study, we examined plasma cytokine and chemokine concentrations in a longitudinal cohort of infants in Papua New Guinea (Oceania; <em>n</em> = 87) across the first four months of life. Using a multiplex assay, concentration of 41 cytokines and chemokines in peripheral blood plasma samples collected at Day of Life (DOL) 0 (i.e., birth), −7, −30, and − 128 were measured. Several cytokines and chemokines that shape cellular immunity demonstrated a statistically significant increase in concentration over the first four months of life, including CXCL10 (5.5-fold), IFNγ (8.8-fold), and IL-2 (1.7-fold). In contrast, other cytokines and chemokines significantly diminished with age, including CCL2 (0.12-fold), CXCL8 (0.35-fold), IL-6 (0.38-fold), and TGFα (0.43-fold). Plasma cytokine and chemokine concentrations appeared to be minimally affected by demographic factors such as birth season, gestational age, sex, or maternal age. The patterns and directionality of these observations largely mirrored those reported in previous cohorts, suggesting universal patterns of plasma cytokine and chemokine trajectories in early life. Overall, understanding early life trajectories of plasma cytokines and chemokines provides insight into human immune development and supports future studies analyzing cytokine trajectories in relation to health and disease.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157076"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145652896","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":"Natural killer cell-related gene signature predicts immune cell infiltration and improved survival in bladder cancer","authors":"Yinglong Huang ,&nbsp;Chen Gong ,&nbsp;Engui Yang ,&nbsp;Haichao Yuan ,&nbsp;Dihao Lv ,&nbsp;Chadanfeng Yang ,&nbsp;Wujie Chen ,&nbsp;Qingyu Wan ,&nbsp;Zhiyong Tan ,&nbsp;Haifeng Wang ,&nbsp;Mingxia Ding ,&nbsp;Senmao Li","doi":"10.1016/j.cyto.2025.157084","DOIUrl":"10.1016/j.cyto.2025.157084","url":null,"abstract":"<div><h3>Background</h3><div>Natural killer (NK) cell-based therapies represent a promising immunotherapeutic approach for cancer treatment. This study aims to identify and evaluate the prognostic significance of NK cell-related genes in bladder cancer (BC).</div></div><div><h3>Methods</h3><div>Using RNA-seq data from The Cancer Genome Atlas (TCGA) BLCA cohort, an NK cell-related gene signature was constructed and validated via multivariate Cox regression. Functional enrichment analyses (GO and KEGG) were conducted to explore associated biological processes. Immune infiltration states were assessed using ESTIMATE and CIBERSORT algorithms. Immunohistochemistry (IHC) and multiplex immunofluorescence (mIF) were performed to validate key findings at the protein level.</div></div><div><h3>Results</h3><div>An eight-gene prognostic signature based on NK cell-related genes was established, enabling stratification of BC patients into high- and low-risk groups. Patients in the high-risk group exhibited significantly worse overall survival (OS) and progression-free survival (PFS). Multivariate analysis confirmed the signature's independence from other clinical variables. The signature was also correlated with distinct immune infiltration patterns, including CD8⁺ T cells, CD4⁺ activated memory T cells, follicular helper T cells, regulatory T cells, activated NK cells, activated dendritic cells, and M0/M2 macrophages. Notably, the key signature gene RAC3 was found to be highly expressed in a subset of tumors. This elevated RAC3 expression was associated with enhanced proliferation (increased Ki67) and reduced infiltration of CD8⁺ T cells and CD56⁺ NK cells, indicating an immunosuppressive microenvironment. Consistently, the TIDE score was significantly lower in the high-risk group, suggesting enhanced potential responsiveness to immunotherapy.</div></div><div><h3>Conclusion</h3><div>The NK cell-related gene signature serves as a robust prognostic biomarker and predictor of immunotherapeutic efficacy in BC. These findings provide new insights into BC biology and facilitate personalized immunotherapy strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157084"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666439","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":"Distinct cytokine signature in juvenile dermatomyositis: linking myositis-specific antibodies and clinical manifestations","authors":"Shuya Kaneko ,&nbsp;Mao Mizuta ,&nbsp;Maho Hatano ,&nbsp;Asami Shimbo ,&nbsp;Hitoshi Irabu ,&nbsp;Reiko Yatabe ,&nbsp;Keiji Akamine ,&nbsp;Yuko Sugita ,&nbsp;Kunio Hashimoto ,&nbsp;Yuichi Yamasaki ,&nbsp;Yasuo Nakagishi ,&nbsp;Masaaki Mori ,&nbsp;Masatoshi Takagi ,&nbsp;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":"2026-01-01","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}

{"title":"Association of toll-like receptors polymorphisms with atopy and asthma symptoms in Latin American children","authors":"Emília Maria Medeiros de Andrade Belitardo ,&nbsp;Cintia Rodrigues Marques ,&nbsp;Thiago Magalhães da Silva ,&nbsp;Eduardo Santos Silva ,&nbsp;Eric Roberto Guimarães Rocha Aguiar ,&nbsp;Mauricio Lima Barreto ,&nbsp;Neuza Maria Alcântara-Neves ,&nbsp;Camila Alexandrina Figueiredo","doi":"10.1016/j.cyto.2025.157073","DOIUrl":"10.1016/j.cyto.2025.157073","url":null,"abstract":"<div><h3>Background</h3><div>Polymorphisms in TLRs genes have been implicated in the physiopathological mechanisms of atopy and asthma.</div></div><div><h3>Objective</h3><div>The aim of this study was to assess the association between polymorphisms on <em>TLRs</em> and atopy/asthma in a highly admixture population of children from Salvador, Bahia, Brazil.</div></div><div><h3>Methods</h3><div>Cross-sectional study. We analyzed 192 SNPs in TLRs genes (<em>TLR1</em>-<em>TLR9</em>) in 1187 children aged 4–11 years living in the urban periphery of Brazil. Bivariate analyses were performed to evaluate the association between <em>TLRs</em> SNPs and asthma syptoms, skin prick test (SPT), and specific IgE to aeroallergens (sIgE). In addition, polytomous logistic regression was used to assess the association between <em>TLRs</em> SNPs and asthma phenotypes, adjusting for sex, age, helminth infection and individual ancestry. Lastly, logistic regression was used to assess gene-environment interactions between <em>TLRs</em> SNPs and different infections in the risk of asthma and atopy.</div></div><div><h3>Results</h3><div>For SPT positivity the most significant associations were identified for rs4833095 in in <em>TLR1</em> (OR: 1.42; 95 % CI: 1.17–1.71; <em>p</em> = 0.00002) and rs1039559 in <em>TLR6</em> (OR: 1.40; CI: 1.15–1.70; <em>p</em> = 0.0009). For sIgE to aeroallergens significant associations were observed for rs5743810 in <em>TLR6</em> (OR: 1.43; 95 % CI: 1.13–1.81 <em>p</em> = 0.004), rs3853839 in <em>TLR7</em> (OR: 1.38; 95 % CI: 1.08–1.76; <em>p</em> = 0.009), and the rs5744139 was the most significantly associated in <em>TLR5</em> gene (OR: 2.0, 95 % CI: 1.17–3.41; <em>p</em> = 0.007). For asthma symptoms significant positive associations were observed for the rs4833095 in <em>TLR1</em> (OR: 1.32; 95 % CI: 1.07–1.62; <em>p</em> = 0.009) and rs2241097 in <em>TLR5</em> (OR: 1.36; 95 % CI: 1.08–1.73; p = 0.009). Furthermore, rs4833095 (OR: 1.38, 95 % CI: 1.03–1.83; <em>p</em> = 0.028) in <em>TLR1</em> and rs2241097 (OR: 1.45; 95 % CI: 1.06–2.00; <em>p</em> = 0.020) in <em>TLR5</em> were positively associated with non-atopic asthma, while rs1039559 (OR: 1.45; 95 % CI: 1.06–2.00; <em>p</em> = 0.036) and rs6531673 (OR: 1.48; 95 % IC: 1.08–2.02; <em>p</em> = 0.014) in <em>TLR6</em> were associated with increased risk for atopic asthma. Gene-environment interaction analyses further revealed that specific infections (e.g., <em>Toxoplasma gondii, HSV, H. pylori, HAV, EBV,</em> and helminths<em>)</em> significantly modified these associations.</div></div><div><h3>Conclusion</h3><div>The results suggest functional significance of polymorphisms on <em>TLR1</em> subfamily, <em>TLR5</em> and <em>TLR6</em> on atopy and asthma, as well as pathogens involved in gene-environment interaction could also play a role in the immunopathological mechanism of atopy and asthma in the studied population.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157073"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569452","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-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 ,&nbsp;Anita Muglia ,&nbsp;Pasqualina Leone ,&nbsp;Eleonora Olivetta ,&nbsp;Sergio Abrignani ,&nbsp;Davide Anzà ,&nbsp;Alessandra Bandera ,&nbsp;Francesca Fortunato ,&nbsp;Andrea Gori ,&nbsp;Renata Grifantini ,&nbsp;Tiziana Lazzarotto ,&nbsp;Vittorio Lodi ,&nbsp;Rosa Prato ,&nbsp;Vincenzo Restivo ,&nbsp;Anna Teresa Palamara ,&nbsp;Paola Stefanelli ,&nbsp;Giorgio Fedele ,&nbsp;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":"2026-01-01","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}

{"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 ,&nbsp;Tong Kong ,&nbsp;Tinghui Wang ,&nbsp;Hua Huang ,&nbsp;Wen Qin ,&nbsp;Baojing Zhao ,&nbsp;Haibo Chen ,&nbsp;Xiudi Wu ,&nbsp;Kaizhe Wang ,&nbsp;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":"2026-01-01","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}

{"title":"Combining single-cell analysis and Mendelian randomization to elucidate the molecular mechanisms of fibronectin-related genes in multiple sclerosis","authors":"Na Zhao ,&nbsp;Mayinuer Maimaiti ,&nbsp;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":"2026-01-01","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}

{"title":"Corrigendum to “Risk factors associated with short-term mortality in patients with candidemia and the predictive value of serum cytokine level” [Cytokine 185 (2025) 156803]","authors":"Xueqing Fang ,&nbsp;Congling Su ,&nbsp;Yan Luo ,&nbsp;Kai Pan ,&nbsp;Jian Lin ,&nbsp;Youliang Song ,&nbsp;Yize Huang ,&nbsp;Xiaochun Hu ,&nbsp;Zhiyong Shen","doi":"10.1016/j.cyto.2025.157077","DOIUrl":"10.1016/j.cyto.2025.157077","url":null,"abstract":"","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157077"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627329","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":"Drug repurposing for cytokine storm: baricitinib, ciclesonide, and acalabrutinib modulate cytokine release in a translational in vitro lymphoblastoid cell line model","authors":"Luka Hiti,&nbsp;Tijana Markovič,&nbsp;Maša Kandušer,&nbsp;Irena Mlinarič-Raščan","doi":"10.1016/j.cyto.2025.157083","DOIUrl":"10.1016/j.cyto.2025.157083","url":null,"abstract":"<div><div>Cytokine storm, a life-threatening hyperinflammatory response seen in severe infections like COVID-19, autoimmune diseases, and certain therapies, remains difficult to treat due to limited approved therapeutics. To support preclinical drug development and repurposing in line with 3R principles, we present a novel <em>in vitro</em> model for screening of cytokine-modulating compounds. Herein, we demonstrate that lymphoblastoid cell lines (LCL cells), derived from healthy donors, provide a translationally relevant and phenotypically diverse platform for cytokine profiling and drug screening. Upon stimulation with PMA/ionomycin, LCL cells exhibited a robust secretion of pro-inflammatory (IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokines, closely mirroring the cytokine profile of activated whole blood. Compared to established immune cell lines THP-1 and Jurkat, LCL cells showed broader cytokine responses and retained interindividual variability.</div><div>We validated the model for cytokine-modulating drug screening using two well-established immunosuppressants, dexamethasone and cyclosporin A. Dexamethasone reduced IL-6 by 21 %, IL-8 by 71 %, IL-12 by 68 %, TNF-α by 83 %, and increased IL-10 by 51 %. Cyclosporin A lowered IL-6 by 34 %, IL-8 by 69 %, IL-10 by 48 %, and TNF-α by 41 %. Subsequently, we tested a panel of clinically investigated COVID-19 therapies, selected based on a comprehensive literature review. Ciclesonide and acalabrutinib showed strong suppression of all measured cytokines by more than 60 %, while baricitinib, which has become a standard of care for severe COVID-19, reduced IL-6 by 70 %, IL-12 by 68 %, and TNF-α by 47 %, but had minimal effect on IL-8. Notably, LCL cells retained interindividual variability, as demonstrated by diverse cytokine as well as divergent NF-κB nuclear translocation responses, supporting the model's capacity to reveal real-world patient heterogeneity.</div><div>Collectively, our findings establish LCL cells as a reproducible, immunologically responsive, and patient-representative platform for cytokine storm research and high-content drug testing, providing both mechanistic insight and translational relevance.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"197 ","pages":"Article 157083"},"PeriodicalIF":3.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145675966","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":"C-reactive protein and albumin: Examining associations with all-cause mortality risk among adults with retinopathy in NHANES","authors":"Xiaohuan Zhao ,&nbsp;Jianfeng Luo ,&nbsp;Xiaoxu Huang ,&nbsp;Shiming Wang ,&nbsp;Hui Cao ,&nbsp;Wenjia Liu ,&nbsp;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":"2026-01-01","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}