Cytokine最新文献

{"title":"Shared inflammation in takotsubo syndrome and sepsis: Lipocalin-2 mediates neutrophil infiltration and cardiac damage","authors":"Yuxi Huang ,&nbsp;Piaorong Zeng ,&nbsp;Tianmin Liu ,&nbsp;Mei Xu ,&nbsp;Wenyi Tang ,&nbsp;Fangyuan Cheng ,&nbsp;Zhijuan Zhou ,&nbsp;Bairong Chen ,&nbsp;Kan Liu ,&nbsp;TouKun Chong ,&nbsp;Jian Chen","doi":"10.1016/j.cyto.2025.157102","DOIUrl":"10.1016/j.cyto.2025.157102","url":null,"abstract":"<div><h3>Background</h3><div>Takotsubo syndrome (TTS) and sepsis often co-occur with poor outcomes, yet their underlying molecular mechanisms remain to be elucidated. Transcriptomic analysis is employed to detect diagnostic biomarkers and reveal shared pathophysiological mechanisms in sepsis-associated TTS.</div></div><div><h3>Methods</h3><div>Myocardial gene expression data (TTS, sepsis, and controls) from GEO were analyzed to identify shared differentially expressed genes. WGCNA and PPI networks were used for candidate gene selection. Key genes were further refined using random forest and LASSO algorithms. Immune cell infiltration was assessed using CIBERSORT. Myocardial injury and gene expression in rat models were evaluated using HE staining, TUNEL assay, immunohistochemistry, qPCR, and Western blotting. Clinical validation was conducted using plasma samples from the China TTS Registry. <em>t</em>-tests and ANOVA were conducted via GraphPad Prism 8 software. A <em>P</em>-value &lt; 0.05 was considered statistically significant.</div></div><div><h3>Results</h3><div>Lipocalin-2 (LCN2) was recognized as an important biomarker through WGCNA, PPI network analysis, and machine learning algorithms, showing strong predictive performance. Its expression was significantly associated with neutrophil infiltration and myocardial injury in TTS. Consistent with the bioinformatics findings, the TTS-sepsis comorbidity model showed elevated mRNA and protein levels of LCN2 in myocardial tissue, accompanied by increased neutrophil infiltration and severe cardiac injury. Clinical validation confirmed elevated plasma LCN2 levels in patients with sepsis-associated TTS, correlating with neutrophil counts, NT-proBNP, and cTnI levels.</div></div><div><h3>Conclusion</h3><div>LCN2 is identified as a key inflammatory mediator linking neutrophil-driven inflammation to myocardial injury in sepsis-associated TTS, with dual potential as a diagnostic biomarker and therapeutic target.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157102"},"PeriodicalIF":3.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877364","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-8-, IL-12-, and VEGF-producing peripheral blood mononuclear cells enable differentiation between vertebral osteomyelitis and degenerative spinal diseases","authors":"Julia Schenk ,&nbsp;Martin Thelen ,&nbsp;Hans Anton Schlößer ,&nbsp;Esther Mahabir","doi":"10.1016/j.cyto.2025.157104","DOIUrl":"10.1016/j.cyto.2025.157104","url":null,"abstract":"<div><div>Vertebral osteomyelitis (VO) is a rare but serious spinal infection that presents significant challenges in early diagnosis and treatment. Diagnostic delays can result in severe complications, including neurological deficits, sepsis, organ failure, and death. In this study, we investigated the immune cell source of candidate cytokines – IL-6, IL-8, IL-12, and VEGF – with the aim of distinguishing VO from degenerative spinal diseases. Peripheral blood samples were collected pre-operatively and 40 to 56 days post-operatively. Cytokine production by major immune cell subsets within peripheral blood mononuclear cells (PBMCs) was analyzed using intracellular flow cytometry. Our findings indicate that pre-operative differentiation between VO and degenerative spinal diseases is feasible, particularly based on IL-8-positive CD8⁺ T-cells, IL-12-positive CD45⁺ lymphocytes, and VEGF-positive cells (including CD45⁺ cells, B-cells, T-cells, and CD8⁺ T-cells).</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157104"},"PeriodicalIF":3.7,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877336","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":"BPI modulates IL-1β-driven inflammation in periodontitis: A case-control study in gingival crevicular fluid","authors":"Kazım Korkmaz,&nbsp;Nezahat Arzu Kayar,&nbsp;Kemal Üstün","doi":"10.1016/j.cyto.2025.157093","DOIUrl":"10.1016/j.cyto.2025.157093","url":null,"abstract":"<div><div>Bactericidal/permeability-increasing protein (BPI) is a neutrophil-derived antimicrobial protein with high affinity for lipopolysaccharide (LPS) of gram-negative bacteria. This study aimed to compare BPI and interleukin-1 beta (IL-1β) levels in gingival crevicular fluid (GCF) between healthy and diseased individuals and to investigate their correlation with clinical parameters. We collected GCF from 50 consecutive ≥18 to &lt;65 years old individuals with generalized periodontitis (P group) and 50 consecutive healthy individuals (H group). Clinical periodontal parameters were documented. IL-1β and BPI levels from GCF were analyzed via ELISA. Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance. GCF levels of BPI and IL-1β were significantly higher in the periodontitis group compared to healthy controls (<em>p</em> &lt; 0.001). Both biomarkers demonstrated strong positive correlations with clinical parameters (<em>p</em> &lt; 0.01). Strong positive correlations were found between GCF BPI levels and GCF IL-1β levels in the P group (P ˂ 0.01). ROC analysis revealed that BPI had a sensitivity of 100 % and an area under the curve (AUC) of 0.76 for detecting periodontitis but low specificity (50 %, AUC = 0.76), while IL-1β had a specificity of 86 % and sensitivity of 72 %. Elevated GCF levels of BPI and its correlation with IL-1β and clinical periodontal measures suggest that BPI might play a dual role in host response by contributing to microbial elimination and regulating inflammation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157093"},"PeriodicalIF":3.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861679","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-7 promotes naïve T cell motility to enable T cell scanning of dendritic cells in the LN","authors":"Janie R. Byrum ,&nbsp;Kimberly A. Morrissey ,&nbsp;David J. Torres ,&nbsp;Sreenivasa Rao Oruganti ,&nbsp;Judy L. Cannon","doi":"10.1016/j.cyto.2025.157105","DOIUrl":"10.1016/j.cyto.2025.157105","url":null,"abstract":"<div><div>IL-7 is a key regulator of naïve T cell homeostasis including T cell development, survival, and proliferation. IL-7 is highly expressed in lymph nodes (LNs), and we investigated the potential for IL-7 to drive naïve T cell movement in LNs. We show that IL-7 can mediate high speed T cell movement in vitro and in LNs. Downstream of IL-7R, T cell motility requires JAK1/3 and STAT5 activation, but mTOR signaling is not required. Using computational modeling and imaging of T cell motion in lymph nodes through two photon microscopy, we find that IL-7R-mediated motility accounts for T cell localization near DCs in the LN, suggesting that IL-7 can regulate naive T cell contacts with DCs. These data demonstrate a novel role for the IL-7/IL-7R pathway in controlling rapid T cell motility, showing that IL-7/IL-7R mediated T cell motion can facilitate efficient T cell-DC interactions in the LN.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157105"},"PeriodicalIF":3.7,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145861637","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":"Group 2 innate lymphoid cells (ILC2s) in childhood allergic diseases: A review of the mechanisms and therapeutic advances","authors":"Yun Zhang ,&nbsp;Yaling Wu ,&nbsp;Yingying Wang ,&nbsp;Haoquan Zhou","doi":"10.1016/j.cyto.2025.157101","DOIUrl":"10.1016/j.cyto.2025.157101","url":null,"abstract":"<div><div>Recent advances in pediatric immunology have clarified the pivotal role of group 2 innate lymphoid cells (ILC2s) in the pathophysiology of childhood allergic diseases. As key components of the innate immune system, ILC2s mediate the initiation and progression of these disorders. Their activation is triggered primarily by epithelial-derived cytokines, whose expression is highly elevated in children with allergies. Upon activation, ILC2s rapidly secrete type 2 cytokines, driving disease-specific pathogenesis. In allergic asthma, airway ILC2 expansion exacerbates eosinophilic inflammation, airway hyperresponsiveness, and remodeling; in allergic rhinitis, nasal mucosal ILC2 activation induces typical symptoms; and in food allergies, intestinal mucosal ILC2s cause epithelial damage and increased permeability, promoting allergic progression. These mechanistic insights have underpinned the development of innovative therapies. Clinical trials have confirmed the efficacy of treatments targeting ILC2-derived cytokines or their receptors: anti-IL-5 monoclonal antibodies (targeting the IL-5 ligand), anti-IL-13 monoclonal antibodies (targeting the IL-13 ligand), and anti-IL-4Rα monoclonal antibodies (targeting IL-4 receptor α and blocking IL-4/IL-13 signaling) are promising treatments for specific childhood allergic diseases. Emerging strategies targeting ILC2 activation pathways and modulating the microbiome to regulate ILC2 activity are under active investigation. Collectively, the past five years of research have improved the understanding of the mechanisms underlying childhood allergic diseases and established new treatment paradigms, with great potential to optimize clinical management and improve the outcomes of pediatric patients with allergies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157101"},"PeriodicalIF":3.7,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837275","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":"Dynamics of the immune cell signature associated with the development of immune-related adverse event: Results from longitudinal immune profiling","authors":"Jiana Chen ,&nbsp;Xiaoyan Si ,&nbsp;Jiaqi Xu ,&nbsp;Ziyue Zhou ,&nbsp;Dan Yang ,&nbsp;Mengyuan Wang ,&nbsp;Li Zhang ,&nbsp;Naixin Liang ,&nbsp;Yunyun Fei ,&nbsp;Xu Jiang ,&nbsp;Huaxia Yang","doi":"10.1016/j.cyto.2025.157103","DOIUrl":"10.1016/j.cyto.2025.157103","url":null,"abstract":"<div><h3>Background</h3><div>The dynamics of peripheral immune cells during the development of immune-related adverse events (irAEs) remain incompletely characterized, underscoring the need to elucidate their temporal patterns to uncover immune disturbances and identify biomarkers.</div></div><div><h3>Methods</h3><div>In this prospective study, patients with lung cancer receiving immune checkpoint inhibitors (ICIs) were enrolled at Peking Union Medical College Hospital and were consecutively followed up for the development of irAEs. Comprehensive immune profiling by multicolor flow cytometry of peripheral blood samples collected at baseline (T0), early (T1, 1-3 weeks) and late (T2, 3-6 months) treatment, and at the onset of irAE (Tae) was performed. We utilized Mfuzz clustering analysis to characterize immune cell trajectories and calculated the change in cell frequencies (ΔT) from T0 to subsequent time points (ΔTae, ΔT1, and ΔT2) to identify time-dependent immune signatures predictive of irAE occurrence, severity, and specific organ involvement.</div></div><div><h3>Results</h3><div>Among the 60 lung cancer patients who received ICIs, 26 (43.3 %) developed irAEs. Mfuzz clustering highlighted the distinct dynamics of CD8^mid T cells and CD14⁺CD16⁻HLA-DR^hi monocytes during ICIs therapy. During early treatment, the irAE group showed a greater increase in CD8⁺CTLA-4⁺ T cells and greater reductions in both total CD8⁺ T cells and double-negative B (DNB) cells. At ΔT2, the irAE group exhibited significantly greater alterations in CD4⁺CD25⁺ T cells, CD4⁺HLA-DR⁺ T cells, CD14⁺CD16⁻HLA-DR^hi monocytes, and CD8^mid T cells. At ΔTae, patients with irAEs exhibited a significant expansion of non-switched memory (NSM) B cells and a reduction in CD3⁺ T cells, whereas non-irAE patients showed opposite trends. Stratified analysis confirmed that the ΔT of NSM B cells, CD8⁺CTLA-4⁺ T cells, DNB cells, CD4⁺CD25⁺ T cells, and CD14⁺CD16⁻HLA-DR^hi monocytes aligned with both clinical severity and specific organ involvement of irAEs.</div></div><div><h3>Conclusion</h3><div>The distinct dynamics of cellular signatures during irAEs development provide potential biomarkers associated with the development of irAEs and shed novel insights into immune disturbance.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157103"},"PeriodicalIF":3.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837307","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":"The role of HMGB1 in central nervous system (CNS) diseases: mechanisms and therapeutic perspectives","authors":"Ou Du,&nbsp;Yi-Jin Wu,&nbsp;Meng-Yang Li,&nbsp;Jun-Rong Du","doi":"10.1016/j.cyto.2025.157099","DOIUrl":"10.1016/j.cyto.2025.157099","url":null,"abstract":"<div><div>Central nervous system (CNS) diseases represent a major global health burden and are among the leading causes of disability and mortality worldwide. The pathological mechanisms underlying CNS disorders are complex and multifactorial, involving processes such as neuroinflammation, oxidative stress, neuronal damage, and synaptic dysfunction. High-mobility group box 1 (HMGB1), a member of the high-mobility group box (HMGB) protein family, is predominantly localized in the nucleus under physiological conditions, where it contributes to DNA repair, transcriptional regulation, and other cellular functions. However, in various CNS pathologies—including stroke, traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), glioblastoma (GBM), epilepsy, depression, multiple sclerosis (MS), and schizophrenia—HMGB1 is released or secreted into the extracellular space. There, it plays a key role in regulating neuroinflammation, cell death, cell migration, and tissue damage and repair, thereby contributing to disease pathogenesis and progression. HMGB1 not only functions as a critical regulator in the progression of CNS diseases but also serves as a biomarker for predicting poor clinical outcomes. Moreover, a growing body of evidence indicates that therapeutic strategies targeting HMGB1 can significantly alleviate pathological damage in various CNS disorders, highlighting its potential as a promising therapeutic target. This review comprehensively summarizes the structure, post-translational modifications, release mechanisms, and receptor systems of HMGB1, along with its roles and mechanisms in CNS diseases. It also discusses the potential of HMGB1 as a biomarker and examines emerging HMGB1-targeted therapeutic strategies, aiming to provide a theoretical foundation for the treatment and drug development of CNS disorders.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157099"},"PeriodicalIF":3.7,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145837306","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":"Clinical observation of anti-PD-1/PD-L1 immunotherapy plus concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma","authors":"Xudong Sun ,&nbsp;Dongmei Wu ,&nbsp;Guangcheng Ding ,&nbsp;Xueying Zhang ,&nbsp;Changli Shi ,&nbsp;Yulong Tian","doi":"10.1016/j.cyto.2025.157096","DOIUrl":"10.1016/j.cyto.2025.157096","url":null,"abstract":"<div><h3>Objective</h3><div>This study analyzed the efficacy of the PD-1 inhibitor Sintilimab combined with concurrent chemoradiotherapy (CCRT) in patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC).</div></div><div><h3>Methods</h3><div>A retrospective study involved 177 individuals with unresectable advanced ESCC, treated with anti-PD-1/PD-L1 immunotherapy combined with CCRT. Patients were categorized into three groups: combined positive score (CPS) ≥ 50, 1 &lt; CPS &lt; 50, and CPS &lt; 1. Clinical data and laboratory markers (carcinoembryonic antigen [CEA] and squamous cell carcinoma antigen [SCC-Ag]) were collected at baseline, 6, 12, and 24 months. PET/CT and CT scans assessed tumor response, ORR, and DCR. Kaplan-Meier curves analyzed the impact of CPS scores on progression-free survival (PFS) and overall survival (OS). Baseline data were matched at a 1:1 ratio by propensity score matching, followed by Cox regression analyses.</div></div><div><h3>Results</h3><div>No noticeable differences were present among the groups regarding gender, tumor location, prior chemotherapy, prior radiotherapy, or laboratory markers. After treatment, CEA and SCC-Ag levels significantly decreased, with the lowest levels observed at 24 months post-treatment. Higher CPS scores were associated with reduced CEA and SCC-Ag levels. PD-L1-positive groups (CPS &gt; 1) had higher ORR and DCR than the PD-L1-negative group. As CPS scores increased, PFS and OS were significantly prolonged. Serum fibrinogen, CEA and SCC-Ag were identified as independent risk factors for OS; Serum CEA and SCC-Ag were independent risk factors affecting PFS.</div></div><div><h3>Conclusion</h3><div>Higher CPS scores are associated with improved PFS and OS in patients with locally advanced ESCC receiving anti-PD-1/PD-L1 immunotherapy combined with CCRT.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157096"},"PeriodicalIF":3.7,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145831883","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":"Relationship between IL-17_A and pneumococcal carriage in children aged under two years: data from a randomised controlled trial in Vietnam","authors":"Zheng Quan Toh ,&nbsp;Yi Ying Ma ,&nbsp;Beth Temple ,&nbsp;Jeremy Anderson ,&nbsp;Hani Hosseini Far ,&nbsp;Thanh V. Phan ,&nbsp;Vo Thi Trang Dai ,&nbsp;Tran Ngoc Huu ,&nbsp;Nguyen Trong Toan ,&nbsp;Kathryn Bright ,&nbsp;Monica Larissa Nation ,&nbsp;Belinda D. Ortika ,&nbsp;Cattram Nguyen ,&nbsp;Heidi Smith-Vaughan ,&nbsp;Catherine Satzke ,&nbsp;Kim Mulholland ,&nbsp;Paul V. Licciardi","doi":"10.1016/j.cyto.2025.157094","DOIUrl":"10.1016/j.cyto.2025.157094","url":null,"abstract":"<div><h3>Objective</h3><div>Pneumococcal carriage is a prerequisite for invasive pneumococcal disease (IPD). Interleukin (IL)-17 A and IL-17 A-producing cells are involved in the clearance of pneumococcal carriage in adults, but their role in children is unclear. This study aims to examine the relationship between IL-17 A, IL-17 A-related cytokines (IL-22, IL-23, IFNγ) and IL-17 A-producing cells and pneumococcal carriage in children aged under two years.</div></div><div><h3>Methods</h3><div>Blood samples (<em>n</em> = 143) collected from unvaccinated children at 18 months (m) of age and nasopharyngeal swabs collected from unvaccinated children at 2, 6, 9, 12, 18, 24 m in the Vietnam Pneumococcal Project (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT01953510</span><svg><path></path></svg></span>) were included in this analysis. Pneumococcal carriage was previously determined. Plasma cytokine concentrations were measured by multiplex bead array or ELISA. Flow cytometry was used to measure IL-17 A/IFNγ-producing cells in peripheral blood mononuclear cells.</div></div><div><h3>Results</h3><div>IL-17 A, IL-22, IL-23 and IFNγ plasma cytokine concentrations were 1.7 to 2.6-fold higher among pneumococcal carriers at 18 m of age compared with non-carriers. Two-to four-fold higher IL-17 A, IL-22, IL-23 concentrations were observed in children carrying two or more pneumococcal serotypes at 18 m compared with children who only carried one pneumococcal serotype or non-carriers. Pneumococcal carriers at 18 m of age had 1.6 to 2-fold higher IL-17 A, IL-22, IL-23 compared with carriers at earlier timepoints (≤12 m). No differences in the frequencies of IL-17 A-producing cells were observed between carriers and non-carriers at 18 m of age. IL-17 A and related cytokines at 18 m of age did not appear to influence clearance of pneumococcus at 24 m of age.</div></div><div><h3>Conclusion</h3><div>Pneumococcal carriage is associated with higher plasma IL-17 A, IL-22 and IL-23 concentrations in children aged under two years.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157094"},"PeriodicalIF":3.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825409","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":"Advances in lipid nanoparticle delivery systems for targeted cytokine immunotherapy in autoimmune disorders","authors":"Dilpreet Singh","doi":"10.1016/j.cyto.2025.157098","DOIUrl":"10.1016/j.cyto.2025.157098","url":null,"abstract":"<div><div>Autoimmune diseases result from dysregulated immune responses, primarily driven by CD4+ T cell imbalances, leading to chronic inflammation and tissue destruction. Conventional cytokine-based therapies, including IL-2 for regulatory T cell (Treg) expansion and IL-6 or IL-17 inhibition for inflammation suppression, have shown promise in modulating immune responses. However, challenges such as systemic toxicity, short half-life, and off-target effects limit their therapeutic efficacy. Lipid nanoparticles (LNPs) have emerged as a next-generation drug delivery platform, offering enhanced cytokine stability, targeted cellular uptake, and controlled release, thereby overcoming limitations associated with free cytokine administration. Preclinical studies have demonstrated that LNP-IL-2 selectively expands Tregs in type 1 diabetes models, while IL-10-loaded LNPs suppress synovial inflammation in rheumatoid arthritis more effectively than conventional cytokine therapies. Optimization of ligand density and affinity on LNP surfaces is emerging as a key determinant of CD4⁺ T cell targeting efficiency. Additionally, LNP-encapsulated siRNA targeting IL-6 and IL-23 has shown superior suppression of inflammatory pathways in lupus and psoriasis. These findings underscore the potential of LNP-mediated cytokine delivery to precisely modulate CD4+ T cell function, restoring immune homeostasis in autoimmune diseases. Despite promising preclinical and early clinical data, challenges remain, including optimizing biodistribution, ensuring selective T cell targeting, and mitigating immune activation risks. This review provides an in-depth analysis of CD4+ T cell subsets in autoimmunity, the advantages of LNP-based cytokine therapies, and their translational potential. The integration of LNP technology into cytokine immunotherapy offers a novel, minimally toxic, and durable approach to reprogramming immune responses, paving the way for precision medicine in autoimmune disease management.</div></div><div><h3>Significance</h3><div>Autoimmune disorders are characterized by chronic inflammation driven by dysregulated cytokine activity. Traditional cytokine therapies often suffer from systemic toxicity and limited targeting precision. This manuscript highlights recent advancements in lipid nanoparticle (LNP) technology for the targeted delivery of cytokines, offering enhanced therapeutic efficacy and safety. By enabling precise modulation of immune responses at disease sites, LNP-based delivery systems represent a transformative approach in immunotherapy. This review underscores the potential of LNPs to overcome current limitations in autoimmune treatment, paving the way for next-generation precision medicine strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157098"},"PeriodicalIF":3.7,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145825443","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}