Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.cyto.2025.157052
Chang Liu, Yi Wei, Fengchuan Jing , Qijian Yi
Background
Kawasaki disease (KD), an acute vasculitis of unclear etiology, is an important contributor to childhood-acquired heart disease due to coronary arterial aneurysms (CAAs). Current diagnosis lacks specific biomarkers, risking delayed treatment. Endocan, a proteoglycan implicated in vascular inflammation, may address this gap. This study evaluates serum endocan in acute KD for its utility in early KD diagnosis and CAA risk prediction.
Method
This prospective cohort study enrolled 79 KD patients and 48 healthy controls. The KD group was further divided into KD with CAA (KD-CAA) and KD non-CAA (KD-NCAA) subgroups. Serum endocan levels were quantified via enzyme-linked immunosorbent assay. Clinical parameters including inflammatory markers were systematically analyzed using SPSS and GraphPad Prism.
Results
Serum endocan levels were significantly elevated in KD patients compared to HCs (median [25th–75th percentile], 1803.69 pg/ml [1478.97–2038.87] vs. 931.73 [815.57–1138.72] pg/ml, P < 0.001), with higher concentrations in KD-CAA versus KD-NCAA (mean ± SD, 1962.43 ± 321.48 vs. 1702.46 ± 458.54 pg/ml, P = 0.024).
Endocan demonstrated excellent performance in distinguishing KD patients from HCs (AUC = 0.915, 95 % CI: 0.863–0.968; sensitivity 88.6 %, specificity 85.4 %). It also showed a modest but statistically significant predictive value for CAAs within the KD cohort (AUC = 0.675, 95 % CI: 0.548–0.801; sensitivity 73.7 %, specificity 58.3 %).
Conclusion
Serum endocan is a high-performance biomarker for differentiating KD from HCs. Despite modest performance in predicting CAAs and undetermined specificity, it may serve as a valuable supportive tool for risk stratification in KD patients.
{"title":"Serum endocan as a dual-function biomarker in Kawasaki disease: early diagnostic potential and prediction of coronary arterial aneurysms","authors":"Chang Liu, Yi Wei, Fengchuan Jing , Qijian Yi","doi":"10.1016/j.cyto.2025.157052","DOIUrl":"10.1016/j.cyto.2025.157052","url":null,"abstract":"<div><h3>Background</h3><div>Kawasaki disease (KD), an acute vasculitis of unclear etiology, is an important contributor to childhood-acquired heart disease due to coronary arterial aneurysms (CAAs). Current diagnosis lacks specific biomarkers, risking delayed treatment. Endocan, a proteoglycan implicated in vascular inflammation, may address this gap. This study evaluates serum endocan in acute KD for its utility in early KD diagnosis and CAA risk prediction.</div></div><div><h3>Method</h3><div>This prospective cohort study enrolled 79 KD patients and 48 healthy controls. The KD group was further divided into KD with CAA (KD-CAA) and KD non-CAA (KD-NCAA) subgroups. Serum endocan levels were quantified via enzyme-linked immunosorbent assay. Clinical parameters including inflammatory markers were systematically analyzed using SPSS and GraphPad Prism.</div></div><div><h3>Results</h3><div>Serum endocan levels were significantly elevated in KD patients compared to HCs (median [25th–75th percentile], 1803.69 pg/ml [1478.97–2038.87] vs. 931.73 [815.57–1138.72] pg/ml, <em>P</em> < 0.001), with higher concentrations in KD-CAA versus KD-NCAA (mean ± SD, 1962.43 ± 321.48 vs. 1702.46 ± 458.54 pg/ml, <em>P</em> = 0.024).</div><div>Endocan demonstrated excellent performance in distinguishing KD patients from HCs (AUC = 0.915, 95 % CI: 0.863–0.968; sensitivity 88.6 %, specificity 85.4 %). It also showed a modest but statistically significant predictive value for CAAs within the KD cohort (AUC = 0.675, 95 % CI: 0.548–0.801; sensitivity 73.7 %, specificity 58.3 %).</div></div><div><h3>Conclusion</h3><div>Serum endocan is a high-performance biomarker for differentiating KD from HCs. Despite modest performance in predicting CAAs and undetermined specificity, it may serve as a valuable supportive tool for risk stratification in KD patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157052"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353137","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}
Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.cyto.2025.157043
Emmerson C.F. de Farias , Patricia B. Carvalho , Luciana M.P.P. do Nascimento , Andreza H.O. Pinheiro , Marília C.B. Alves , Kíssila M.M. Machado-Ferraro , Larisse F.Q. Aires , Luana G. Dias , Mayara M.M. Machado , Michaelle J.D. Serrão , Raphaella R. Gomes , Sara M.P. de Moraes , Gabriela C.L. Pontes , Railana D.F.P. Carvalho , Elaine B.G.P. Nascimento , Cristiane T.C. Silva , Adriana M.B. de Sousa , Lêda L. da Silva , Nathália K.F. Barbosa , Anna L.M. Machado , Marta C. Monteiro
Background
Multiple organ dysfunction syndrome (MODS) remains a major cause of morbidity and mortality in pediatric intensive care units (PICUs), particularly when triggered by SARS-CoV-2 or bacterial sepsis. This study aimed to investigate the association between inflammatory and oxidative stress biomarkers and the development and outcome of MODS in critically ill children with confirmed SARS-CoV-2 or bacterial infections.
Methods
In this prospective, single-center cohort study (May 2020–December 2024), 62 pediatric patients (29 days to <18 years) were stratified into three groups: SARS-CoV-2 without MODS (n = 22), SARS-CoV-2 with MODS (n = 20), and bacterial MODS (n = 20). Circulating cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A) and oxidative stress markers (GSH, TBARS, TEAC) were quantified at PICU admission and on day 5. Associations with organ dysfunction and 28-day mortality were assessed using non-parametric statistical analyses and Kaplan-Meier survival estimates.
Results
MODS groups exhibited on day 1 sustained elevations in TNF-α, IFN-γ, and IL-17A—most pronounced in bacterial MODS (Group 3; p < 0.0001). IFN-γ was notably increased in viral MODS (Group 2). Group 3 also showed marked elevations in IL-6, IL-2, and IL-10 (p < 0.0001). By day 5, both MODS groups demonstrated significant reduced GSH and TEAC and elevated TBARS, the most severe in Group 3. In contrast, Group 1 exhibited stable cytokine profiles and preserved antioxidant status throughout. Non-survivors showed persistently elevated IL-6, TNF-α, IFN-γ, and IL-17A, coupled with sustained depletion of GSH and TEAC, and increased TBARS levels (all p < 0.0001). IL-6 and IFN-γ were particularly elevated in non-survivors with bacterial and viral MODS, respectively. Biomarker trajectories diverged between survivors and non-survivors by day 5, with failure to normalize immune-redox profiles associated with mortality. Accessible indices such as NLR, CAR, and VIS correlated with biomarker levels and disease severity. Kaplan–Meier analysis confirmed reduced survival in MODS groups (p = 0.0005).
Conclusions
A distinct cytokine and oxidative stress signature—marked by early and sustained elevations in IL-6, TNF-α, IFN-γ, IL-17A, and TBARS, and depletion of GSH and TEAC—is associated with mortality in pediatric MODS. Bacterial MODS was distinguished by the most severe immune-redox imbalance. Integrated immune-redox profiling offers prognostic value and may inform precision-targeted interventions, particularly in resource-limited settings.
{"title":"IL-6, IFN-γ, IL-17A elevations and glutathione depletion predict severe MODS and mortality in critically ill children with COVID-19 and bacterial sepsis: a prospective cohort study from the Brazilian Amazon","authors":"Emmerson C.F. de Farias , Patricia B. Carvalho , Luciana M.P.P. do Nascimento , Andreza H.O. Pinheiro , Marília C.B. Alves , Kíssila M.M. Machado-Ferraro , Larisse F.Q. Aires , Luana G. Dias , Mayara M.M. Machado , Michaelle J.D. Serrão , Raphaella R. Gomes , Sara M.P. de Moraes , Gabriela C.L. Pontes , Railana D.F.P. Carvalho , Elaine B.G.P. Nascimento , Cristiane T.C. Silva , Adriana M.B. de Sousa , Lêda L. da Silva , Nathália K.F. Barbosa , Anna L.M. Machado , Marta C. Monteiro","doi":"10.1016/j.cyto.2025.157043","DOIUrl":"10.1016/j.cyto.2025.157043","url":null,"abstract":"<div><h3>Background</h3><div>Multiple organ dysfunction syndrome (MODS) remains a major cause of morbidity and mortality in pediatric intensive care units (PICUs), particularly when triggered by SARS-CoV-2 or bacterial sepsis. This study aimed to investigate the association between inflammatory and oxidative stress biomarkers and the development and outcome of MODS in critically ill children with confirmed SARS-CoV-2 or bacterial infections.</div></div><div><h3>Methods</h3><div>In this prospective, single-center cohort study (May 2020–December 2024), 62 pediatric patients (29 days to <18 years) were stratified into three groups: SARS-CoV-2 without MODS (<em>n</em> = 22), SARS-CoV-2 with MODS (<em>n</em> = 20), and bacterial MODS (n = 20). Circulating cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A) and oxidative stress markers (GSH, TBARS, TEAC) were quantified at PICU admission and on day 5. Associations with organ dysfunction and 28-day mortality were assessed using non-parametric statistical analyses and Kaplan-Meier survival estimates.</div></div><div><h3>Results</h3><div>MODS groups exhibited on day 1 sustained elevations in TNF-α, IFN-γ, and IL-17A—most pronounced in bacterial MODS (Group 3; <em>p</em> < 0.0001). IFN-γ was notably increased in viral MODS (Group 2). Group 3 also showed marked elevations in IL-6, IL-2, and IL-10 (p < 0.0001). By day 5, both MODS groups demonstrated significant reduced GSH and TEAC and elevated TBARS, the most severe in Group 3. In contrast, Group 1 exhibited stable cytokine profiles and preserved antioxidant status throughout. Non-survivors showed persistently elevated IL-6, TNF-α, IFN-γ, and IL-17A, coupled with sustained depletion of GSH and TEAC, and increased TBARS levels (all <em>p</em> < 0.0001). IL-6 and IFN-γ were particularly elevated in non-survivors with bacterial and viral MODS, respectively. Biomarker trajectories diverged between survivors and non-survivors by day 5, with failure to normalize immune-redox profiles associated with mortality. Accessible indices such as NLR, CAR, and VIS correlated with biomarker levels and disease severity. Kaplan–Meier analysis confirmed reduced survival in MODS groups (<em>p</em> = 0.0005).</div></div><div><h3>Conclusions</h3><div>A distinct cytokine and oxidative stress signature—marked by early and sustained elevations in IL-6, TNF-α, IFN-γ, IL-17A, and TBARS, and depletion of GSH and TEAC—is associated with mortality in pediatric MODS. Bacterial MODS was distinguished by the most severe immune-redox imbalance. Integrated immune-redox profiling offers prognostic value and may inform precision-targeted interventions, particularly in resource-limited settings.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157043"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353182","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}
Pub Date : 2025-12-01Epub Date: 2025-10-08DOI: 10.1016/j.cyto.2025.157047
Leonardo Lima Cardoso, Delva Fonseca Lamec Thyares, Ana Letícia Monteiro Fernandes, Rosália Santos Ferreira, Shayenne Eduarda Ramos Vanderley, Fernando Cézar Comberlang, Fernanda Silva Almeida, Tatjana de Souza Lima Keesen
Leishmania infantum, the main causative agent of zoonotic visceral leishmaniasis, persists and proliferates within host monocytes and macrophages. Numerous studies have focused on developing innovative therapies, as conventional treatments are hampered by high toxicity, drug resistance, and relapse. In recent decades, anti-leishmanial immunotherapy — aimed at triggering or modulating the host's immune response — has gained momentum, with various immunomodulators being tested in experimental and clinical settings. However, achieving effective immunotherapy remains challenging, as it requires a delicate balance between enhancing protective, parasite-specific immune responses and avoiding harmful hyperinflammation. In this context, we evaluated quercetin, a natural flavonoid with reported immunomodulatory properties, alone and in combination with Amphotericin B (AmB), against Leishmania infantum promastigotes and during human monocyte infection. Infected and non-infected PBMCs were assessed for parasite viability and cytotoxicity; monocyte infection rates, reactive oxygen species (ROS), nitric oxide (NO) production, and cytokine profiles. Quercetin showed significant anti-promastigote activity and, in combination with AmB, enhanced parasite death, indicating synergistic effects. It also reduced monocyte infection rates, enhanced ROS production, and downregulated levels of IL-6, IL-10, and IL-17, without altering NO production. These findings support the concept of quercetin as a dual-action agent, exerting direct anti-leishmanial effects while fine-tuning the host immune response. By promoting beneficial immunological pathways and dampening potentially deleterious cytokines, quercetin exemplifies the “trapeze act” of immunotherapy, suggesting its potential as an adjuvant to conventional chemotherapy in visceral leishmaniasis.
{"title":"Quercetin enhances amphotericin B activity and regulates ROS and cytokine production in human monocytes infected by Leishmania infantum","authors":"Leonardo Lima Cardoso, Delva Fonseca Lamec Thyares, Ana Letícia Monteiro Fernandes, Rosália Santos Ferreira, Shayenne Eduarda Ramos Vanderley, Fernando Cézar Comberlang, Fernanda Silva Almeida, Tatjana de Souza Lima Keesen","doi":"10.1016/j.cyto.2025.157047","DOIUrl":"10.1016/j.cyto.2025.157047","url":null,"abstract":"<div><div><em>Leishmania infantum</em>, the main causative agent of zoonotic visceral leishmaniasis, persists and proliferates within host monocytes and macrophages. Numerous studies have focused on developing innovative therapies, as conventional treatments are hampered by high toxicity, drug resistance, and relapse. In recent decades, anti-leishmanial immunotherapy — aimed at triggering or modulating the host's immune response — has gained momentum, with various immunomodulators being tested in experimental and clinical settings. However, achieving effective immunotherapy remains challenging, as it requires a delicate balance between enhancing protective, parasite-specific immune responses and avoiding harmful hyperinflammation. In this context, we evaluated quercetin, a natural flavonoid with reported immunomodulatory properties, alone and in combination with Amphotericin B (AmB), against <em>Leishmania infantum</em> promastigotes and during human monocyte infection. Infected and non-infected PBMCs were assessed for parasite viability and cytotoxicity; monocyte infection rates, reactive oxygen species (ROS), nitric oxide (NO) production, and cytokine profiles. Quercetin showed significant anti-promastigote activity and, in combination with AmB, enhanced parasite death, indicating synergistic effects. It also reduced monocyte infection rates, enhanced ROS production, and downregulated levels of IL-6, IL-10, and IL-17, without altering NO production. These findings support the concept of quercetin as a dual-action agent, exerting direct anti-leishmanial effects while fine-tuning the host immune response. By promoting beneficial immunological pathways and dampening potentially deleterious cytokines, quercetin exemplifies the “trapeze act” of immunotherapy, suggesting its potential as an adjuvant to conventional chemotherapy in visceral leishmaniasis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157047"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145256892","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}
Pub Date : 2025-12-01Epub Date: 2025-10-27DOI: 10.1016/j.cyto.2025.157063
Amisha Mahur , Bhoomika M. Patel
Cardiac cachexia, a severe consequence of heart failure, is marked by progressive weight loss due to skeletal and cardiac muscle wasting. This complex condition involves nutritional deficiencies, gut dysfunction, hormonal imbalances, and a critical disruption in muscle protein metabolism. However, chronic inflammation in the heart failure is the key driver, triggering the release of cytokines like TNF-α, IL-6, IL-1, IL-10 and TGF-β. These cytokines significantly impact muscle metabolism, promoting protein breakdown while hindering protein synthesis. Elevated TNF-α levels induce anorexia, worsening weight loss, and muscle depletion. IL-6 acts as a potent muscle-wasting agent, upregulating protein degradation via the ubiquitin-proteasome system. Similarly, IL-1 activates pathways that promote protein breakdown and suppress cell proliferation. TGF-β, despite its diverse functions, contributes to muscle atrophy by increasing protein degradation. In contrast, the anti-inflammatory cytokine IL-10 promotes protein synthesis by suppressing pathways that normally inhibit it. Understanding these cytokine actions provides valuable insights into cardiac cachexia and paves the way for targeted therapies aimed at modulating these pathways to prevent or reverse muscle wasting in heart failure. In this review, we will describe the pathophysiology of cardiac cachexia and the role of various cytokines in cardiac cachexia which is released due to inflammation.
{"title":"Inflammation and inflammatory cytokines in cardiac cachexia: an incendiary issue","authors":"Amisha Mahur , Bhoomika M. Patel","doi":"10.1016/j.cyto.2025.157063","DOIUrl":"10.1016/j.cyto.2025.157063","url":null,"abstract":"<div><div>Cardiac cachexia, a severe consequence of heart failure, is marked by progressive weight loss due to skeletal and cardiac muscle wasting. This complex condition involves nutritional deficiencies, gut dysfunction, hormonal imbalances, and a critical disruption in muscle protein metabolism. However, chronic inflammation in the heart failure is the key driver, triggering the release of cytokines like TNF-α, IL-6, IL-1, IL-10 and TGF-β. These cytokines significantly impact muscle metabolism, promoting protein breakdown while hindering protein synthesis. Elevated TNF-α levels induce anorexia, worsening weight loss, and muscle depletion. IL-6 acts as a potent muscle-wasting agent, upregulating protein degradation via the ubiquitin-proteasome system. Similarly, IL-1 activates pathways that promote protein breakdown and suppress cell proliferation. TGF-β, despite its diverse functions, contributes to muscle atrophy by increasing protein degradation. In contrast, the anti-inflammatory cytokine IL-10 promotes protein synthesis by suppressing pathways that normally inhibit it. Understanding these cytokine actions provides valuable insights into cardiac cachexia and paves the way for targeted therapies aimed at modulating these pathways to prevent or reverse muscle wasting in heart failure. In this review, we will describe the pathophysiology of cardiac cachexia and the role of various cytokines in cardiac cachexia which is released due to inflammation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157063"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145385471","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}
Pub Date : 2025-12-01Epub Date: 2025-10-17DOI: 10.1016/j.cyto.2025.157058
Zhi Li , Wen Qin , Xiudi Wu , Mingcai Li , Yan Li
Background: Polymyositis (PM) and dermatomyositis (DM) are two common subtypes of idiopathic inflammatory myopathies (IIM). The concentration of serum interleukin (IL)-41 in patients with PM/DM has not been reported. This study aims to investigate the levels of IL-41 in the serum of individuals diagnosed with PM/DM.
Methods: A total of 118 participants were enrolled in the study, comprising 80 patients with PM/DM and 38 healthy controls (HC). Comprehensive clinical data for each participant were collected through physical examinations and detailed clinical histories. The levels of IL-41 were quantified using the enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was employed to examine the relationship between IL-41 levels and various clinical parameters. The diagnostic potential of IL-41 was assessed using the receiver operating characteristic (ROC) curve.
Results: Serum IL-41 levels were significantly elevated in PM/DM patients with interstitial lung disease (ILD) compared to HC [1001.03 (572.95, 1604.83) pg/mL vs 361.03 (302.24, 541.06) pg/mL, P < 0.0001]. Furthermore, a significant difference was also observed in serum IL-41 levels between PM/DM patients without ILD and HC [561.81 (407.94, 827.34) pg/mL vs 361.03 (302.24, 541.06) pg/mL, P = 0.0139]. IL-41 exhibits substantial diagnostic potential for PM/DM, and its combination with lactate dehydrogenase enhances diagnostic efficacy. Moreover, IL-41 acts as an independent risk factor for the onset of PM/DM.
Conclusions: This study revealed that serum IL-41 levels are elevated in patients with PM/DM, suggesting that IL-41 could serve as a novel biomarker for the identification of these conditions.
{"title":"Unveiling IL-41: A novel biomarker for polymyositis and dermatomyositis diagnosis","authors":"Zhi Li , Wen Qin , Xiudi Wu , Mingcai Li , Yan Li","doi":"10.1016/j.cyto.2025.157058","DOIUrl":"10.1016/j.cyto.2025.157058","url":null,"abstract":"<div><div><em>Background:</em> Polymyositis (PM) and dermatomyositis (DM) are two common subtypes of idiopathic inflammatory myopathies (IIM). The concentration of serum interleukin (IL)-41 in patients with PM/DM has not been reported. This study aims to investigate the levels of IL-41 in the serum of individuals diagnosed with PM/DM.</div><div><em>Methods:</em> A total of 118 participants were enrolled in the study, comprising 80 patients with PM/DM and 38 healthy controls (HC). Comprehensive clinical data for each participant were collected through physical examinations and detailed clinical histories. The levels of IL-41 were quantified using the enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was employed to examine the relationship between IL-41 levels and various clinical parameters. The diagnostic potential of IL-41 was assessed using the receiver operating characteristic (ROC) curve.</div><div><em>Results:</em> Serum IL-41 levels were significantly elevated in PM/DM patients with interstitial lung disease (ILD) compared to HC [1001.03 (572.95, 1604.83) pg/mL vs 361.03 (302.24, 541.06) pg/mL, <em>P</em> < 0.0001]. Furthermore, a significant difference was also observed in serum IL-41 levels between PM/DM patients without ILD and HC [561.81 (407.94, 827.34) pg/mL vs 361.03 (302.24, 541.06) pg/mL, <em>P</em> = 0.0139]. IL-41 exhibits substantial diagnostic potential for PM/DM, and its combination with lactate dehydrogenase enhances diagnostic efficacy. Moreover, IL-41 acts as an independent risk factor for the onset of PM/DM.</div><div><em>Conclusions:</em> This study revealed that serum IL-41 levels are elevated in patients with PM/DM, suggesting that IL-41 could serve as a novel biomarker for the identification of these conditions.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157058"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317987","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}
Gestational diabetes mellitus (GDM) is associated with low-grade inflammation which can contribute to insulin resistance and dysregulated glucose metabolism. Anakinra is a recombinant form of IL-1 receptor antagonist (IL-1Ra) that has shown promise in the control of several inflammatory diseases. The present study aimed to evaluate the potential of Anakinra in the control of inflammation and glucose metabolism in a genetic model of GDM.
Pregnant C57BL/KsJdb/+ (db/+) mice were used as the murine model of GDM and the glucose metabolism, insulin resistance as well as levels of inflammatory mediators were evaluated. The populations of Th17 and Treg cells were also analyzed in spleens of mice. Some GDM-associated parameters were studied in offspring along with an evaluation of oxidative stress in the liver and placenta.
Anakinra improved the glucose tolerance and insulin sensitivity of GDM mice and controlled the weight gain of the pregnant mice. The population of Th17 cells as key mediators of inflammatory processes declined in the Anakinra-received mice and the serum levels of pro-inflammatory cytokines as well as the activation of the NF-κB pathway declined accordingly. Besides, the infiltration of T-cells into the placenta was diminished in Anakinra-treated mice.
Anakinra demonstrated a potential for control of GDM by targeting low-grade inflammation and improving glucose metabolism. Regarding the fair properties of small molecules that render them suitable therapeutic tools, Anakinra might be a candidate therapeutic for the control of GDM more efficiently.
{"title":"Anakinra ameliorates insulin resistance and inflammation in a murine model of gestational diabetes through downregulation of Th17 responses Anakinra for the treatment of GDM in mice","authors":"Lingyan Zhang , Fudan Huang , Shaik Althaf Hussain , Yi Tian","doi":"10.1016/j.cyto.2025.157039","DOIUrl":"10.1016/j.cyto.2025.157039","url":null,"abstract":"<div><div>Gestational diabetes mellitus (GDM) is associated with low-grade inflammation which can contribute to insulin resistance and dysregulated glucose metabolism. Anakinra is a recombinant form of IL-1 receptor antagonist (IL-1Ra) that has shown promise in the control of several inflammatory diseases. The present study aimed to evaluate the potential of Anakinra in the control of inflammation and glucose metabolism in a genetic model of GDM.</div><div>Pregnant C57BL/KsJdb/+ (db/+) mice were used as the murine model of GDM and the glucose metabolism, insulin resistance as well as levels of inflammatory mediators were evaluated. The populations of Th17 and Treg cells were also analyzed in spleens of mice. Some GDM-associated parameters were studied in offspring along with an evaluation of oxidative stress in the liver and placenta.</div><div>Anakinra improved the glucose tolerance and insulin sensitivity of GDM mice and controlled the weight gain of the pregnant mice. The population of Th17 cells as key mediators of inflammatory processes declined in the Anakinra-received mice and the serum levels of pro-inflammatory cytokines as well as the activation of the NF-κB pathway declined accordingly. Besides, the infiltration of T-cells into the placenta was diminished in Anakinra-treated mice.</div><div>Anakinra demonstrated a potential for control of GDM by targeting low-grade inflammation and improving glucose metabolism. Regarding the fair properties of small molecules that render them suitable therapeutic tools, Anakinra might be a candidate therapeutic for the control of GDM more efficiently.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157039"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263708","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}
Pub Date : 2025-12-01Epub Date: 2025-09-21DOI: 10.1016/j.cyto.2025.157027
XueyingWang , Jun Hu
Background: Postoperative renal function assessment in pediatric kidney transplant recipients faces the challenge of insufficient sensitivity of traditional indicators. T1-mapping, a non-invasive imaging technique, can quantify changes in the microscopic structure of renal tissue. However, its application in the pediatric population and its relationship with serum cytokines remain unclear. This study hypothesized that T1-mapping can quantitatively assess early renal microstructural damage in pediatric kidney transplant recipients and that T1 values correlate with the activation of immune-inflammatory responses (reflected by serum cytokine levels). It aimed to explore the value of T1-mapping in evaluating renal function and its mechanistic association with inflammatory responses.
Materials and Methods: A total of 31 pediatric kidney transplant recipients (observation group, Obs group) and 31 healthy children (control group, Ctrl group) were enrolled. In the Obs group, T1-mapping was performed at 1, 3, and 6 months post-transplantation to measure T1 values in the renal cortex, medulla, and whole kidney. Serum creatinine (SCr), glomerular filtration rate (GFR), and other renal function indicators were assessed, along with CD4+, CD8+ lymphocyte counts, and levels of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Based on the 6-month postoperative prognosis, participants were divided into the good prognosis group (GPG, n = 20) and poor prognosis group (PPG, n = 11).
Results: The T1 values of the renal cortex, medulla, and whole kidney in the Obs group were significantly higher than those in the Ctrl group (P < 0.05). Specifically, the cortical T1 value in the PPG was (1820 ± 110) ms, significantly higher than that in the GPG (1650 ± 80) ms (P < 0.05). The SCr in the PPG was (220 ± 35) μmol/L, and the GFR was (22 ± 5) mL/min/1.73m2, both significantly worse than the GPG (85 ± 12 μmol/L, 78 ± 10 mL/min/1.73m2, P < 0.05). The CD4+/CD8+ ratio in the GPG (1.49 ± 0.21) was higher than that in the PPG (0.87 ± 0.15), while the CD8+ cell count (550 ± 60 × 106/L) in the GPG was lower than that in the PPG (780 ± 75 × 106/L, P < 0.05). Levels of IL-6 (28.8 ± 6.5 pg/mL) and TNF-α (45.5 ± 8.3 pg/mL) in the PPG were significantly higher than those in the GPG (12.5 ± 3.0 pg/mL, 18.2 ± 4.1 pg/mL, P < 0.05).
Conclusion: T1-mapping technology can quantitatively assess changes in renal function following pediatric kidney transplantation, with increased T1 values closely associated with immune-inflammatory activation and renal function damage. Serum cytokine levels reflect the intensity of the inflammatory response, providing new evidence for postoperative monitoring and intervention.
背景：儿童肾移植受者术后肾功能评估面临传统指标敏感性不足的挑战。t1成像是一种非侵入性成像技术，可以量化肾组织微观结构的变化。然而，其在儿童人群中的应用及其与血清细胞因子的关系尚不清楚。本研究假设T1定位可以定量评估儿童肾移植受者早期肾脏微结构损伤，并且T1值与免疫炎症反应的激活相关（通过血清细胞因子水平反映）。旨在探讨t1制图在评估肾功能中的价值及其与炎症反应的机制关联。材料与方法：选取31例儿童肾移植受者（观察组，Obs组）和31例健康儿童（对照组，Ctrl组）作为研究对象。在Obs组，在移植后1、3和6个月进行T1制图，测量肾皮质、髓质和全肾的T1值。评估血清肌酐（SCr）、肾小球滤过率（GFR）和其他肾功能指标，以及CD4+、CD8+淋巴细胞计数，以及白细胞介素-6 （IL-6）和肿瘤坏死因子-α (TNF-α)等细胞因子水平。根据术后6个月预后分为预后良好组（GPG, n = 20）和预后不良组（PPG, n = 11）。结果：Obs组肾皮质、髓质、全肾T1值均显著高于对照组（P < 0.05）。其中，PPG组皮层T1值为（1820±110）ms，显著高于GPG组（1650±80）ms （P < 0.05）。PPG的SCr为（220±35）μmol/L， GFR为（22±5）mL/min/1.73m2，均显著低于GPG（85±12 μmol/L, 78±10 mL/min/1.73m2, P < 0.05）。GPG中CD4+/CD8+比值（1.49±0.21）高于PPG(0.87±0.15)，而CD8+细胞计数（550±60 × 106/L）低于PPG（780±75 × 106/L, P < 0.05）。PPG组IL-6（28.8±6.5 pg/mL）、TNF-α（45.5±8.3 pg/mL）水平显著高于GPG组（12.5±3.0 pg/mL、18.2±4.1 pg/mL, P < 0.05）。结论：T1制图技术可以定量评估儿童肾移植术后肾功能的变化，T1值升高与免疫炎症激活和肾功能损害密切相关。血清细胞因子水平反映炎症反应的强度，为术后监测和干预提供新的依据。
{"title":"T1-mapping quantitative assessment of renal function and changes in serum cytokine levels after renal transplantation in children","authors":"XueyingWang , Jun Hu","doi":"10.1016/j.cyto.2025.157027","DOIUrl":"10.1016/j.cyto.2025.157027","url":null,"abstract":"<div><div>Background: Postoperative renal function assessment in pediatric kidney transplant recipients faces the challenge of insufficient sensitivity of traditional indicators. T1-mapping, a non-invasive imaging technique, can quantify changes in the microscopic structure of renal tissue. However, its application in the pediatric population and its relationship with serum cytokines remain unclear. This study hypothesized that T1-mapping can quantitatively assess early renal microstructural damage in pediatric kidney transplant recipients and that T1 values correlate with the activation of immune-inflammatory responses (reflected by serum cytokine levels). It aimed to explore the value of T1-mapping in evaluating renal function and its mechanistic association with inflammatory responses.</div><div>Materials and Methods: A total of 31 pediatric kidney transplant recipients (observation group, Obs group) and 31 healthy children (control group, Ctrl group) were enrolled. In the Obs group, T1-mapping was performed at 1, 3, and 6 months post-transplantation to measure T1 values in the renal cortex, medulla, and whole kidney. Serum creatinine (SCr), glomerular filtration rate (GFR), and other renal function indicators were assessed, along with CD4+, CD8+ lymphocyte counts, and levels of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Based on the 6-month postoperative prognosis, participants were divided into the good prognosis group (GPG, <em>n</em> = 20) and poor prognosis group (PPG, <em>n</em> = 11).</div><div>Results: The T1 values of the renal cortex, medulla, and whole kidney in the Obs group were significantly higher than those in the Ctrl group (<em>P</em> < 0.05). Specifically, the cortical T1 value in the PPG was (1820 ± 110) ms, significantly higher than that in the GPG (1650 ± 80) ms (<em>P</em> < 0.05). The SCr in the PPG was (220 ± 35) μmol/L, and the GFR was (22 ± 5) mL/min/1.73m<sup>2</sup>, both significantly worse than the GPG (85 ± 12 μmol/L, 78 ± 10 mL/min/1.73m<sup>2</sup>, <em>P</em> < 0.05). The CD4+/CD8+ ratio in the GPG (1.49 ± 0.21) was higher than that in the PPG (0.87 ± 0.15), while the CD8+ cell count (550 ± 60 × 10<sup>6</sup>/L) in the GPG was lower than that in the PPG (780 ± 75 × 10<sup>6</sup>/L, <em>P</em> < 0.05). Levels of IL-6 (28.8 ± 6.5 pg/mL) and TNF-α (45.5 ± 8.3 pg/mL) in the PPG were significantly higher than those in the GPG (12.5 ± 3.0 pg/mL, 18.2 ± 4.1 pg/mL, <em>P</em> < 0.05).</div><div>Conclusion: T1-mapping technology can quantitatively assess changes in renal function following pediatric kidney transplantation, with increased T1 values closely associated with immune-inflammatory activation and renal function damage. Serum cytokine levels reflect the intensity of the inflammatory response, providing new evidence for postoperative monitoring and intervention.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157027"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145107834","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}
Endometriosis is a chronic inflammatory condition often associated with infertility. The role of granzymes as cytotoxic proteases and immune regulators in endometriosis remains poorly understood. This study evaluated serum and peritoneal fluid levels of granzymes A, B, and K in women with endometriosis and their links to disease severity.
Methodology
An observational study of 87 infertile women undergoing diagnostic laparoscopy, including 44 with endometriosis and 43 benign gynecologic controls. Granzyme levels were measured using ELISA and correlated with clinical parameters.
Results
Serum GrB and GrK were significantly higher in women with endometriosis, particularly in advanced stages. Peritoneal fluid revealed reduced GrA and increased GrB in the endometriosis group. Serum GrB and GrK levels correlated positively with rASRM adhesion and endometriosis severity scores, while GrB levels correlated inversely with the Endometriosis Infertility Index (EFI) score, indicating their role in predicting infertility. Combining serum GrB and GrK effectively differentiated endometriosis from control, highlighting their diagnostic potential.
Conclusion
Elevated serum GrB and GrK levels suggest their involvement in endometriosis pathogenesis and infertility. These findings highlight granzymes as promising biomarkers for disease severity, diagnosis, and targeted therapy in endometriosis management.
{"title":"Extracellular granzyme B and K are associated with endometriosis severity in infertile women","authors":"Fadhil Ahsan , Budi Santoso , Nanda Yuli Rahmawati , Fidyah Nanda Alditia , Alfin Firasy Mufid , M.Y. Ardianta Widyanugraha , Ashon Sa'adi , Sri Ratna Dwiningsih , Arif Tunjungseto","doi":"10.1016/j.cyto.2025.157045","DOIUrl":"10.1016/j.cyto.2025.157045","url":null,"abstract":"<div><h3>Background</h3><div>Endometriosis is a chronic inflammatory condition often associated with infertility. The role of granzymes as cytotoxic proteases and immune regulators in endometriosis remains poorly understood. This study evaluated serum and peritoneal fluid levels of granzymes A, B, and K in women with endometriosis and their links to disease severity.</div></div><div><h3>Methodology</h3><div>An observational study of 87 infertile women undergoing diagnostic laparoscopy, including 44 with endometriosis and 43 benign gynecologic controls. Granzyme levels were measured using ELISA and correlated with clinical parameters.</div></div><div><h3>Results</h3><div>Serum GrB and GrK were significantly higher in women with endometriosis, particularly in advanced stages. Peritoneal fluid revealed reduced GrA and increased GrB in the endometriosis group. Serum GrB and GrK levels correlated positively with rASRM adhesion and endometriosis severity scores, while GrB levels correlated inversely with the Endometriosis Infertility Index (EFI) score, indicating their role in predicting infertility. Combining serum GrB and GrK effectively differentiated endometriosis from control, highlighting their diagnostic potential.</div></div><div><h3>Conclusion</h3><div>Elevated serum GrB and GrK levels suggest their involvement in endometriosis pathogenesis and infertility. These findings highlight granzymes as promising biomarkers for disease severity, diagnosis, and targeted therapy in endometriosis management.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157045"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218247","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}
Pub Date : 2025-12-01Epub Date: 2025-10-16DOI: 10.1016/j.cyto.2025.157057
Huriye Ezveci , Sukran Dogru , Fikriye Karanfil Yaman , Pelin Bahçeci , Hatice Bedia Yildiz , Meltem Uyaner Kan , İbrahim Kilinç , Kazım Gezginç
Objective
The study aims to evaluate the prediction of gestational diabetes mellitus (GDM) by proinflammatory resistin, chemerin, and progranulin, as well as anti-inflammatory adipokines omentin and IL-10, in maternal serum during the first trimester.
Material method
This prospective case-control study was performed in the obstetric unit of the university hospital from January 2023 to July 2024. Maternal serum samples from the study cases were collected during the first-trimester screening test to analyze resistin, chemerin, progranulin, omentin, and IL-10 levels. The cases were subsequently categorized into groups diagnosed with GDM and those not diagnosed between 24 and 28 weeks. Clinical and laboratory assessments were conducted.
Results
The study included a total of 160 pregnant women. 38 of these patients had GDM, and 122 had control cases. In the serum samples taken in the first trimester, resistin, chemerin, and IL-10 levels did not create a statistically significant difference in the GDM and control groups (p > 0.05). Statistical differences were observed between the groups in progranulin and omentin levels (p = 0.042, p = 0.004, respectively). For predicting GDM, the optimum cut-off value was 83.5 for progranulin (sensitivity: 57.9 %, specificity: 63.9 %, PPV: 33.3 %, NPV: 83 %) and 2.5 for omentin (sensitivity: 73.7 %, specificity: 58.2 %, PPV: 35.4 %, NPV: 87.7 %).
Conclusion
First-trimester progranulin and omentin levels may be useful in excluding GDM, but they lack sufficient power to diagnose it.
{"title":"First-trimester prediction of gestational diabetes mellitus using resistin, chemerin, progranulin, omentin, and IL-10","authors":"Huriye Ezveci , Sukran Dogru , Fikriye Karanfil Yaman , Pelin Bahçeci , Hatice Bedia Yildiz , Meltem Uyaner Kan , İbrahim Kilinç , Kazım Gezginç","doi":"10.1016/j.cyto.2025.157057","DOIUrl":"10.1016/j.cyto.2025.157057","url":null,"abstract":"<div><h3>Objective</h3><div>The study aims to evaluate the prediction of gestational diabetes mellitus (GDM) by proinflammatory resistin, chemerin, and progranulin, as well as anti-inflammatory adipokines omentin and IL-10, in maternal serum during the first trimester.</div></div><div><h3>Material method</h3><div>This prospective case-control study was performed in the obstetric unit of the university hospital from January 2023 to July 2024. Maternal serum samples from the study cases were collected during the first-trimester screening test to analyze resistin, chemerin, progranulin, omentin, and IL-10 levels. The cases were subsequently categorized into groups diagnosed with GDM and those not diagnosed between 24 and 28 weeks. Clinical and laboratory assessments were conducted.</div></div><div><h3>Results</h3><div>The study included a total of 160 pregnant women. 38 of these patients had GDM, and 122 had control cases. In the serum samples taken in the first trimester, resistin, chemerin, and IL-10 levels did not create a statistically significant difference in the GDM and control groups (<em>p</em> > 0.05). Statistical differences were observed between the groups in progranulin and omentin levels (<em>p</em> = 0.042, <em>p</em> = 0.004, respectively). For predicting GDM, the optimum cut-off value was 83.5 for progranulin (sensitivity: 57.9 %, specificity: 63.9 %, PPV: 33.3 %, NPV: 83 %) and 2.5 for omentin (sensitivity: 73.7 %, specificity: 58.2 %, PPV: 35.4 %, NPV: 87.7 %).</div></div><div><h3>Conclusion</h3><div>First-trimester progranulin and omentin levels may be useful in excluding GDM, but they lack sufficient power to diagnose it.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157057"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312038","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}
Pub Date : 2025-12-01Epub Date: 2025-10-22DOI: 10.1016/j.cyto.2025.157061
Jianna Mao, Yuhou Shen, Hongyang Qi
Background
Helicobacter pylori infection is a major risk factor for the development of peptic ulcer disease and associated cancers, posing a significant public health concern. Peroxisome proliferator-activated receptor gamma (PPARγ) has been implicated in mucosal healing and may modulate H. pylori–induced gastric injury. In this study, we investigated the role of PPARγ in the progression of H. pylori–induced gastric ulceration.
Method
The potential association between PPARγ level and H. pylori infection rate was firstly analyzed with clinical samples. Then the effects of PPARγ activation on H. pylori–induced inflammation in human gastric epithelial cells (HGECs) were evaluated using CCK-8 assays for cell viability and immunofluorescence for inflammatory markers. The expression of PPARγ downstream effectors, including TLRs/NF-κB axis was also detected.
Results
Clinical analysis revealed that H. pylori infection significantly increased the risk of gastric ulcer development. PPARγ levels were inversely correlated with H. pylori infection rate and with the concentrations of IL-6, IL-1β, and TNF-α. In HGECs, lipopolysaccharide (LPS) treatment induced abnormal cell viability and heightened inflammatory responses, both of which were attenuated by the PPARγ agonist pioglitazone. Pioglitazone selectively promoted apoptosis in LPS-treated cells. At the molecular level, LPS increased expression of TLR2, TLR4, and TLR5, leading to NF-κB pathway activation; PPARγ activation suppressed both TLR expression and NF-κB signaling, coinciding with reduced cytokine release.
Conclusions
The current study demonstrates that PPARγ activation exerts anti–H. pylori effects during gastric ulcer progression by inhibiting the TLR/NF-κB signaling pathway.
{"title":"Inflammation in gastric epithelium associated with infection of Helicobacter pylori is induced by inhibited PPARγ pathway: the key role of TLRs/NF-κB axis","authors":"Jianna Mao, Yuhou Shen, Hongyang Qi","doi":"10.1016/j.cyto.2025.157061","DOIUrl":"10.1016/j.cyto.2025.157061","url":null,"abstract":"<div><h3>Background</h3><div><em>Helicobacter pylori</em> infection is a major risk factor for the development of peptic ulcer disease and associated cancers, posing a significant public health concern. Peroxisome proliferator-activated receptor gamma (PPARγ) has been implicated in mucosal healing and may modulate <em>H. pylori</em>–induced gastric injury. In this study, we investigated the role of PPARγ in the progression of <em>H. pylori</em>–induced gastric ulceration.</div></div><div><h3>Method</h3><div>The potential association between PPARγ level and <em>H. pylori</em> infection rate was firstly analyzed with clinical samples. Then the effects of PPARγ activation on <em>H. pylori</em>–induced inflammation in human gastric epithelial cells (HGECs) were evaluated using CCK-8 assays for cell viability and immunofluorescence for inflammatory markers. The expression of PPARγ downstream effectors, including TLRs/NF-κB axis was also detected.</div></div><div><h3>Results</h3><div>Clinical analysis revealed that <em>H. pylori</em> infection significantly increased the risk of gastric ulcer development. PPARγ levels were inversely correlated with <em>H. pylori</em> infection rate and with the concentrations of IL-6, IL-1β, and TNF-α. In HGECs, lipopolysaccharide (LPS) treatment induced abnormal cell viability and heightened inflammatory responses, both of which were attenuated by the PPARγ agonist pioglitazone. Pioglitazone selectively promoted apoptosis in LPS-treated cells. At the molecular level, LPS increased expression of TLR2, TLR4, and TLR5, leading to NF-κB pathway activation; PPARγ activation suppressed both TLR expression and NF-κB signaling, coinciding with reduced cytokine release.</div></div><div><h3>Conclusions</h3><div>The current study demonstrates that PPARγ activation exerts anti–<em>H. pylori</em> effects during gastric ulcer progression by inhibiting the TLR/NF-κB signaling pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157061"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353162","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}
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