Cytokine最新文献

{"title":"IL-6 trans-signaling activates the TGF-β pathway via soluble factors in difficult-to-treat rheumatoid arthritis joint fluid","authors":"Yang Bei-bei ,&nbsp;Liu Ji-zan ,&nbsp;Rui Hong-bing ,&nbsp;Xue Juan ,&nbsp;Xiao Hua","doi":"10.1016/j.cyto.2026.157113","DOIUrl":"10.1016/j.cyto.2026.157113","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the impact of joint fluid (JF) from difficult-to-treat (D2T)rheumatoid arthritis (RA) patients on joint inflammation.</div></div><div><h3>Methods</h3><div>We compared the clinical characteristics of D2T RA and non-D2T RA patients. Joint fluid samples from patients with various forms of chronic arthritis were analyzed. The activation of IL-6/STAT3 and TGF-β/SMAD3 pathways in normal Fibroblast-like synoviocytes (FLS) after exposure to D2T RA joint fluid was also evaluated, along with the effects of pathway inhibitors on cell proliferation, apoptosis, invasion, and migration.</div></div><div><h3>Results</h3><div>D2T RA joint fluid showed elevated levels of IL-6 and TGF-β1 compared to non-D2T RA, osteoarthritis, and ankylosing spondylitis samples. The IL-6/STAT3 pathway was directly activated in normal FLS upon exposure to D2T RA joint fluid, while the TGF-β/SMAD3 pathway was indirectly activated through IL-6 trans-signaling, resulting in increased proliferation, migration, invasion, and anti-apoptotic properties of FLS. The use of SMAD3 Inhibitory Selective 3 (SIS3) to block the TGF-β/SMAD3 pathway partially mitigated the effects of D2T RA joint fluid. Tocilizumab and the soluble glycoprotein 130 Fc fusion protein (sgp130Fc) successfully inhibited IL-6–associated pSMAD3 activation, highlighting a mediating role of IL-6.</div></div><div><h3>Conclusion</h3><div>The joint fluid milieu may contribute to persistent synovial activation in D2T RA, and highlights IL-6 trans-signaling as a potential therapeutic target in this context. In addition, timely aspiration of joint fluid from patients with D2T RA may help modulate the local inflammatory microenvironment and could represent a supportive strategy in disease management.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157113"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923710","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":"Urinary interleukin-37 as a suggested protective biomarker of renal prognosis in autosomal dominant polycystic kidney disease","authors":"Kai Hu ,&nbsp;Jiaxin Chen ,&nbsp;Bo Yang ,&nbsp;Lili Fu ,&nbsp;Qing Yao ,&nbsp;Jing Xu ,&nbsp;Mengjin Li ,&nbsp;Nanmei Liu ,&nbsp;Cheng Xue ,&nbsp;Zhiguo Mao","doi":"10.1016/j.cyto.2026.157116","DOIUrl":"10.1016/j.cyto.2026.157116","url":null,"abstract":"<div><h3>Background</h3><div>Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst expansion and chronic inflammation. Interleukin-37 (IL-37) is an anti-inflammatory cytokine, but its role in ADPKD remains unclear. This study aimed to evaluate IL-37 expression in ADPKD patients and assess its clinical relevance in disease severity and renal prognosis.</div></div><div><h3>Methods</h3><div>IL-37 expression in kidney tissues and cell lines was examined by real-time PCR, Western blot, and immunofluorescence. IL-37 levels were measured by ELISA. This retrospective observational cohort study analyzed longitudinal follow-up data of ADPKD patients using Cox proportional hazards models to explore the prognostic value of IL-37 for progression to end-stage kidney disease (ESKD).</div></div><div><h3>Results</h3><div>78 ADPKD patients and 20 normal controls were included. IL-37 expression was significantly elevated in kidney tissues, cyst fluid, serum, and urine from ADPKD patients compared with normal controls. Urinary IL-37, adjusted for creatinine (uIL-37/uCr), rose with advancing CKD stages, and it showed a positive correlation with tubular injury markers—NGAL, L-FABP, MCP-1, and α1-MG—and a negative correlation with eGFR and hemoglobin levels. After adjusting for baseline eGFR, age, and inflammation-associated biomarkers (MCP1), elevated urinary IL-37 was independently associated with better kidney survival (HR = 0.954, 95% CI: 0.912–0.998, <em>P</em> = 0.041), suggesting a protective role in ADPKD progression.</div></div><div><h3>Conclusions</h3><div>IL-37 is elevated in ADPKD, reflecting inflammation and tubular injury in disease pathogenesis. Despite higher levels in advanced disease, urinary IL-37 independently predicts better renal survival, suggesting its potential as both a disease activity marker and prognostic indicator.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157116"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146016851","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":"Danshensu sodium attenuates pyroptosis in ischemic stroke by targeting the HMGB1/RAGE axis and downstream NLRP3/GSDMD/ASC/Caspase-1 pathway","authors":"Jing Zhang ,&nbsp;Dandan Liu ,&nbsp;Chuanyu Jia ,&nbsp;Shuyang Wang ,&nbsp;Yuhui Li","doi":"10.1016/j.cyto.2026.157109","DOIUrl":"10.1016/j.cyto.2026.157109","url":null,"abstract":"<div><h3>Background</h3><div>Danshensu Sodium (DSS-S), the sodium salt of a principal water-soluble active compound from <em>Salvia miltiorrhiza</em>, was investigated for its effects on cerebral ischemic-reperfusion (I/R) injury and the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>Neuroprotection by DSS-S was evaluated <em>in vivo</em> using a transient middle cerebral artery occlusion (tMCAO) model in male C57BL/6J mice and <em>in vitro</em> using an oxygen-glucose deprivation/reperfusion (OGD/R) model in Neuro-2a mouse neuroblastoma cells.</div></div><div><h3>Results</h3><div>High-mobility group box 1 (HMGB1) was identified as a key target of DSS-S. Following I/R or OGD/R, levels of IL-1β, IL-6, TNF-α, IL-18, and HMGB1 were significantly elevated in both mouse serum and cell culture supernatant, and these increases were substantially attenuated by DSS-S treatment. DSS-S reduced cytoplasmic HMGB1 accumulation, promoted its nuclear retention, down-regulated the receptor for advanced glycation end-products (RAGE), and weakened the HMGB1-RAGE interaction. Pyroptosis was activated in both tMCAO and OGD/R models, and DSS-S intervention effectively inhibited pyroptosis by suppressing the HMGB1/RAGE signaling pathway and NLRP3 inflammasome activation.</div></div><div><h3>Conclusion</h3><div>DSS-S exerts neuroprotective effects against cerebral I/R injury <em>in vivo</em> and reduces OGD/R-induced injury <em>in vitro</em>. The protection is mediated through inhibition of pyroptosis, achieved by targeting the HMGB1/RAGE axis and suppressing NLRP3 inflammasome activation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157109"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923709","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":"Enhanced lymphotoxin alpha DNA hypermethylation and correlation with genetic polymorphism in rheumatoid arthritis among the Chinese population","authors":"Jingjing Song,&nbsp;Zhen Liu,&nbsp;Xiaohong Xu,&nbsp;Yanni Wang,&nbsp;Fan Yang,&nbsp;Ting Zhang,&nbsp;Yunqing Zhang,&nbsp;Yufei Bi,&nbsp;Zhenglun Pan","doi":"10.1016/j.cyto.2026.157117","DOIUrl":"10.1016/j.cyto.2026.157117","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is a multifactorial autoimmune disorder characterized by persistent inflammation and joint destruction. Despite advances in understanding RA's immunopathology, its epigenetic regulation remains underexplored, particularly in diverse populations. This study aims to bridge this gap by examining lymphotoxin alpha (LTA) DNA methylation in a Chinese cohort and exploring the relationship with gene polymorphism.</div></div><div><h3>Methods</h3><div>This study involved 145 RA patients and 140 age-matched healthy controls from Qingdao, China. We analyzed DNA methylation in the LTA gene using bisulfite sequencing and assessed SNP genotypes with high-resolution melting analysis. Statistical correlations were performed using SPSS to link methylation patterns with clinical indicators of RA severity.</div></div><div><h3>Results</h3><div>Significantly higher methylation levels were observed at several CpG sites within the LTA gene in RA patients compared to controls. These methylation patterns were positively correlated with clinical measures such as erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score-28, suggesting their relevance in RA pathophysiology. The CC genotype of rs2009658 was associated with elevated methylation at multiple CpG sites within the LTA gene, as well as the TT genotype of rs2229094.</div></div><div><h3>Conclusions</h3><div>LTA DNA methylation is a potential inflammatory indicator and therapeutic target for RA. The rs2009658 CC genotype and rs2229094 TT genotype are susceptible genotypes associated with LTA hypermethylation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157117"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974947","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":"IGF-1 upregulates IL-36α expression via NF-κB and p38 MAPK pathways to promote inflammation in thyroid eye disease","authors":"Jun Huang,&nbsp;Chao Wu,&nbsp;Yulan Zhang,&nbsp;Yifan Wu,&nbsp;Feiran Wang,&nbsp;Yi Zhou,&nbsp;Lu Shi","doi":"10.1016/j.cyto.2026.157115","DOIUrl":"10.1016/j.cyto.2026.157115","url":null,"abstract":"<div><h3>Background</h3><div>Thyroid eye disease (TED), the most prevalent extrathyroidal manifestation of Graves' disease, involves insulin-like growth factor-1 (IGF-1) as a central pathogenic factor. Interleukin-36α (IL-36α), a key member of the IL-1 superfamily, has emerged as a critical regulator in autoimmune diseases.</div></div><div><h3>Objective</h3><div>To investigate the role of IL-36α in TED pathogenesis and elucidate the molecular mechanisms by which IGF-1 regulates IL-36α expression.</div></div><div><h3>Methods</h3><div>Specimens including serum and orbital connective tissues were obtained from TED subjects and controls. Orbital fibroblasts (OFs) were isolated from patients with TED. Enzyme-linked immunosorbent assay, immunohistochemistry, quantitative real-time PCR and Western blot analysis were performed.</div></div><div><h3>Results</h3><div>We demonstrated that IL-36α levels increased in the circulation and orbital connective tissues of patients with TED compared with controls, and levels were positively correlated with the clinical activity score. In vitro, IGF-1 induced IL-36α expression in OFs through NF-κB and p38 MAPK pathway activation. Furthermore, we revealed that IL-36α stimulation promoted robust pro-inflammatory cytokine production, which was effectively blocked by Interleukin-36 receptor antagonist (IL-36Ra) treatment.</div></div><div><h3>Conclusions</h3><div>IGF-1 upregulates IL-36α expression via NF-κB and p38 MAPK pathways to promote inflammation in TED, with IL-36α levels significantly correlating with disease activity. These findings identify IL-36α as a promising biomarker and therapeutic target for TED management.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157115"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145923711","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":"Sennoside A alleviates fungal keratitis by modulating inflammation and immune responses through the caspase-1/GSDMD pathway","authors":"Mengzhu Liu ,&nbsp;Nan Jiang ,&nbsp;Shiqi Song ,&nbsp;Qiang Xu,&nbsp;Ling Wang,&nbsp;Fenglei Wang,&nbsp;Xiaomei Wan,&nbsp;Xiaoyan Sun,&nbsp;Chengye Che","doi":"10.1016/j.cyto.2026.157120","DOIUrl":"10.1016/j.cyto.2026.157120","url":null,"abstract":"<div><h3>Purpose</h3><div>This study was designed to systematically investigate the therapeutic efficacy and mechanistic underpinnings of the natural plant-derived anthraquinone glycoside, sennoside A (SA), in fungal keratitis.</div></div><div><h3>Methods</h3><div>We rigorously assessed the safety and therapeutic efficacy of SA in primary peripheral blood neutrophils, THP-1 macrophages, and mouse corneas. Safety was evaluated using CCK-8 viability assays and corneal fluorescein sodium staining. Therapeutic outcomes and immune responses were determined through clinical scoring, hematoxylin–eosin (H&amp;E) staining, immunofluorescence (IF), myeloperoxidase (MPO) activity assays, and flow cytometry. Anti-inflammatory mechanisms were investigated by quantifying caspase-1 and GSDMD protein expression, together with downstream IL-1β and IL-18 mRNA and protein levels, using quantitative real-time PCR (qRT-PCR), Western blotting, and IF. Meanwhile, we explored the translational potential of combining SA with the antifungal agent natamycin.</div></div><div><h3>Results</h3><div>SA (100 μg/mL) showed no toxicity to cells, corneas, or organs. It significantly reduced corneal clouding, swelling, and clinical severity scores in infected mice. Treatment also decreased the recruitment of pathogenic immune cells (neutrophils/macrophages) and shifted macrophages toward a repair-promoting phenotype. SA inhibited the caspase-1/GSDMD inflammatory pathway, leading to reduced levels of key inflammatory cytokines (IL-1β, IL-18). When combined with natamycin, SA provided better protection than either treatment alone.</div></div><div><h3>Conclusion</h3><div>SA effectively mitigated fungal keratitis-induced damage by suppressing harmful inflammation and modulating immune responses. Its synergistic action with existing antifungal therapies underscores its promising clinical potential.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157120"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146035402","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":"Th2-M2 polarization in the pathogenesis of adenoid hypertrophy is predominantly characterized by type 2 inflammation","authors":"Zheng Gu ,&nbsp;Zong-tong Lin ,&nbsp;Zhong-jie Yang ,&nbsp;Qi-Yuan Zou ,&nbsp;En-Mei Liu ,&nbsp;Wei Kou ,&nbsp;Ping Wei","doi":"10.1016/j.cyto.2026.157108","DOIUrl":"10.1016/j.cyto.2026.157108","url":null,"abstract":"<div><h3>Background</h3><div>Adenoid hypertrophy (AH) is a common condition in children that can lead to various complications and significantly affect their growth and development. However, the underlying pathogenesis is not fully understood. This study aims to investigate Th2-M2 polarization in the pathogenesis of AH, focusing on a predominant type 2 inflammatory pattern.</div></div><div><h3>Methods</h3><div>We recruited control participants without AH and patients with AH combined with allergic rhinitis (AR), and investigated the predominant inflammatory type in AH with concomitant AR by measuring the Th cell sub-populations and the expression of their key transcription factors, and the levels of type 2 inflammatory factors IL-4 and IL-13 in the adenoid tissue. Additionally, the distribution and quantity of M2 macrophages (M2) in the adenoid tissue were detected to determine their involvement in the pathogenesis of type 2 inflammation-predominant AH. Finally, differentially expressed genes were identified through transcriptome RNA sequencing, followed by their functional validation. A co-culture system of CD68⁺ macrophages and CD4⁺ T cells was established, with IL-4 and dermatophagoides farinae intervention used to explore the role of Th2-M2 polarization in the pathogenesis of type 2 inflammatory predominant AH.</div></div><div><h3>Results</h3><div>We found that the predominant inflammatory subtypes in AH with concomitant AR were type 2 inflammation and Th17-type inflammation. Further investigation revealed that M2 is involved in the pathogenesis of type 2 inflammation- predominant AH. Transcriptome RNA sequencing identified differentially expressed genes CHI3L2, SOCS1, and STAT6. Functional validation revealed that the Th2-M2 polarization crosstalk promote M2 polarization and may participate in the pathogenesis of AH through the STAT6/SOCS1 pathway. Furthermore, CHI3L2 was found to be highly expressed in the adenoid tissue with a predominant type 2 inflammatory profile. The co-culture of CD68+ macrophages and CD4⁺ T cells along with IL-4 and dermatophagoides farina intervention further validated the sequencing results.</div></div><div><h3>Conclusion</h3><div>The Th2-M2 polarization may be involved in the pathogenesis of type 2 inflammatory predominant AH, possibly through the STAT6/SOCS1 pathway, which promotes the polarization of M2 macrophages, increases cellular proliferation in the adenoid tissue, and drives the disease process. CHI3L2 was highly expressed in type 2 inflammation–predominant AH and may serve as a promising biomarker candidate for this inflammatory subtype. Further studies are required to determine whether CHI3L2 functionally contributes to adenoid hypertrophy or immune-cell proliferation, which could serve as a therapeutic target.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157108"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145908816","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-γ (IFNγ), a double-edge sword that affects prognoses in critically ill patients: A prospective study","authors":"Guangjian Wang ,&nbsp;Hui Lian ,&nbsp;Hongmin Zhang ,&nbsp;Xiaoting Wang ,&nbsp;Shuyang Zhang ,&nbsp;Xuefeng Ni","doi":"10.1016/j.cyto.2026.157110","DOIUrl":"10.1016/j.cyto.2026.157110","url":null,"abstract":"<div><h3>Background</h3><div>Abnormal inflammatory responses and viral infections play a critical role in the pathogenesis of critical illnesses. Critically ill patients frequently develop multiple organ dysfunction syndrome (MODS), a key determinant of clinical outcomes and a marker of poor prognosis. Interferon-γ (IFNγ), an important inflammatory regulatory cytokine, may serve as a more accurate indicator of viral infection severity and holds potential as a predictor of MODS and prognosis in critically ill patients.</div></div><div><h3>Purpose</h3><div>To evaluate the association between IFNγ levels and clinical outcomes in critically ill patients.</div></div><div><h3>Methods</h3><div>This prospective study, conducted from January 1 to May 31, 2023, at Peking Union Medical College Hospital, used data from electronic medical records to collect baseline characteristics, ICU parameters, laboratory tests, and clinical outcomes. MODS was diagnosed on the basis of Sequential Organ Failure Assessment (SOFA) scores. Generalized Additive Models were employed to explore linear and nonlinear associations, while survival analyses were performed using the Kaplan–Meier method.</div></div><div><h3>Results</h3><div>A total of 208 patients were analyzed. IFNγ levels demonstrated a significant positive linear correlation with MODS in both sepsis (odds ratio [OR] 1.041, 95% confidence interval [CI]: 0.962–1.126) and non-sepsis (OR 1.025, 95% CI: 0.907–1.157) subgroups (intergroup <em>P</em> &lt; 0.001). The relationship between IFNγ levels and 28-day mortality followed a U-shaped curve, with a threshold of 5.3 ng/mL. In the sepsis subgroup, patients with low IFNγ levels exhibited poorer prognoses compared with those with high IFNγ levels (<em>P</em> = 0.021). No significant difference in prognosis was observed between procalcitonin (PCT) subgroups (<em>P</em> = 0.087). Among patients with elevated IFNγ levels, a positive correlation between PCT and 28-day mortality was identified (OR 1.098, 95% CI: 0.815–1.481).</div></div><div><h3>Conclusion</h3><div>IFNγ is strongly associated with MODS and prognosis in critically ill patients, highlighting its potential as a biomarker for predicting MODS occurrence and patient outcomes. These findings underscore the clinical value of IFNγ in critical care, providing a foundation for further research in this area.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"199 ","pages":"Article 157110"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964525","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":"2026-02-01","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":"Functional impact of IL-36γ rs28947206/rs28947207 and IL-17 a rs2275913 polymorphisms in polycystic ovary syndrome: Novel insights from the Iraqi population","authors":"Halah Amer Abduljabbar ,&nbsp;Methaq J. Al-Jboori ,&nbsp;Manal Taha Al-Obeidi ,&nbsp;Majid Mohammed Mahmood","doi":"10.1016/j.cyto.2026.157106","DOIUrl":"10.1016/j.cyto.2026.157106","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) affects 4–21 % of reproductive-aged women, with elevated prevalence in Iraq. It involves chronic inflammation and dysregulated pro-inflammatory cytokines. This study investigates serum IL-17 A levels and its rs2275913 polymorphism, alongside the novel relevance of IL-36γ and its rs28947206/rs28947207 variants in PCOS pathogenesis. A total of 178 women underwent clinical, hormonal, and cytokine profiling. Genetic analysis was performed on a subset (<em>n</em> = 63) using PCR-Sanger sequencing. PCOS patients showed significantly elevated IL-17 A (48.7 ± 12.3 vs 32.1 ± 8.9 pg/ml) and IL-36γ (142.6 ± 28.4 vs 58.9 ± 14.7 pg/ml) levels (<em>p</em> &lt; 0.001), with IL-36γ demonstrating superior diagnostic accuracy (AUC = 0.970 vs 0.851). Hormonal dysregulation included reduced FSH and elevated testosterone, AMH, LH, LH/FSH ratio, prolactin, and BMI (<em>P</em> &lt; 0.05). Clinical features such as hirsutism, acne, alopecia, menstrual irregularities, and poor pregnancy outcomes were more prevalent (P &lt; 0.05). IL-36γ rs28947206/rs28947207 variants were monomorphic in all subjects, marking the first report of these SNPs in PCOS. <em>IL-17 A</em> rs2275913 was significantly associated with PCOS, with the A allele (OR = 4.71) and AA genotype (OR = 10.71) linked to altered AMH, prolactin, and LH/FSH levels. IL-36γ is a promising diagnostic biomarker, while IL-17 A rs2275913 represents a genetic risk factor for PCOS in the Iraqi population.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"198 ","pages":"Article 157106"},"PeriodicalIF":3.7,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916389","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}