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}
Pub Date : 2025-12-01Epub Date: 2025-10-09DOI: 10.1016/j.cyto.2025.157040
B.C. Wang , S. Chaki , H. Taufiq , K. Sikder , S.K. Shukla , K. Rafiq
Sepsis-induced cardiac dysfunction is a major contributor to the high morbidity and mortality rates seen in septic patients, with those suffering from concurrent cardiac dysfunction experiencing mortality rates up to 90 %. This study elucidates the role of allograft inflammatory factor-1 (AIF-1) in sepsis-induced cardiac dysfunction, using a cecal ligation and puncture (CLP) model in both wild-type (WT) and AIF-1 knockout (-/-) C57BL/6 mice. We specifically examined AIF-1's expression across genders and its impact on cardiac function and inflammation.
Results indicate a significant gender-specific upregulation of AIF-1 in female murine hearts during septic shock, suggesting a protective role of this molecule in mitigating cardiac dysfunction. In contrast, AIF-1 knockout female mice exhibited exacerbated cardiac dysfunction compared to their wild-type counterparts, as evidenced by decreased ejection fraction and fractional shortening, increased expression of pro-inflammatory cytokines (TNF-α, IL-6), and heightened cardiac inflammation. Moreover, AIF-1 deletion reduced macrophage infiltration in the heart, underscoring its role in modulating immune responses during septic challenges.
These findings highlight the protective effects of AIF-1 in female mice and suggest its potential as a therapeutic target for sepsis-induced cardiac dysfunction. Understanding AIF-1's mechanisms may facilitate the development of gender-specific treatments to improve outcomes in sepsis, particularly by leveraging its role in enhancing cardiac resilience and modulating inflammation.
{"title":"Sepsis-induced cardiac dysfunction: Gender bias role of allograft inflammatory factor-1","authors":"B.C. Wang , S. Chaki , H. Taufiq , K. Sikder , S.K. Shukla , K. Rafiq","doi":"10.1016/j.cyto.2025.157040","DOIUrl":"10.1016/j.cyto.2025.157040","url":null,"abstract":"<div><div>Sepsis-induced cardiac dysfunction is a major contributor to the high morbidity and mortality rates seen in septic patients, with those suffering from concurrent cardiac dysfunction experiencing mortality rates up to 90 %. This study elucidates the role of allograft inflammatory factor-1 (AIF-1) in sepsis-induced cardiac dysfunction, using a cecal ligation and puncture (CLP) model in both wild-type (WT) and AIF-1 knockout (<sup>-/-</sup>) C57BL/6 mice. We specifically examined AIF-1's expression across genders and its impact on cardiac function and inflammation.</div><div>Results indicate a significant gender-specific upregulation of AIF-1 in female murine hearts during septic shock, suggesting a protective role of this molecule in mitigating cardiac dysfunction. In contrast, AIF-1 knockout female mice exhibited exacerbated cardiac dysfunction compared to their wild-type counterparts, as evidenced by decreased ejection fraction and fractional shortening, increased expression of pro-inflammatory cytokines (TNF-α, IL-6), and heightened cardiac inflammation. Moreover, AIF-1 deletion reduced macrophage infiltration in the heart, underscoring its role in modulating immune responses during septic challenges.</div><div>These findings highlight the protective effects of AIF-1 in female mice and suggest its potential as a therapeutic target for sepsis-induced cardiac dysfunction. Understanding AIF-1's mechanisms may facilitate the development of gender-specific treatments to improve outcomes in sepsis, particularly by leveraging its role in enhancing cardiac resilience and modulating inflammation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157040"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145263707","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: 2025-10-01DOI: 10.1016/j.cyto.2025.157042
Antonio Piralla , Sabrina Gioria , Giuditta Guerrini , Greta Petazzoni , Guglielmo Ferrari , Alessandro Ferrari , Federica Giardina , Federica Bergami , Anita Orlando , Silvia Mongodi , Federico Capra Marzani , Mara De Amici , Giorgia Testa , Luigi Calzolai , Fausto Baldanti
This study explores the immune response dynamics in critically ill SARS-CoV-2 patients compared to non-SARS-CoV-2 controls both hospitalized in intensive care unit (ICU), focusing on localized and systemic inflammatory profiles to identify patterns linked to clinical outcomes. A cohort of ICU patients (37 SARS-CoV-2 positive, 17 controls) underwent bronchoalveolar lavage (BAL) and plasma analysis to assess inflammatory markers using a multiplex assay. SARS-CoV-2 patients showed distinct clinical and immunological features, including prolonged ICU stays and elevated markers of systemic inflammation. Cluster analysis revealed subgroup-specific immune signatures, with COVID-19 survivors demonstrating coordinated cytokine/chemokine interactions suggestive of adaptive immune regulation, while non-survivors exhibited dysregulated profiles indicative of maladaptive inflammation. The study underscores the spatial segregation of immune responses, with lung-specific inflammation in BAL contrasting with systemic profiles, highlighting the importance of tissue-targeted monitoring. These findings suggest that immune profiling could inform stratification for tailored immunomodulatory therapies, advancing precision approaches in critical care for severe SARS-CoV-2 infections.
{"title":"Differential cytokine and chemokine signatures in bronchoalveolar lavage and plasma predict clinical outcomes of COVID-19 patients hospitalized in intensive care unit","authors":"Antonio Piralla , Sabrina Gioria , Giuditta Guerrini , Greta Petazzoni , Guglielmo Ferrari , Alessandro Ferrari , Federica Giardina , Federica Bergami , Anita Orlando , Silvia Mongodi , Federico Capra Marzani , Mara De Amici , Giorgia Testa , Luigi Calzolai , Fausto Baldanti","doi":"10.1016/j.cyto.2025.157042","DOIUrl":"10.1016/j.cyto.2025.157042","url":null,"abstract":"<div><div>This study explores the immune response dynamics in critically ill SARS-CoV-2 patients compared to non-SARS-CoV-2 controls both hospitalized in intensive care unit (ICU), focusing on localized and systemic inflammatory profiles to identify patterns linked to clinical outcomes. A cohort of ICU patients (37 SARS-CoV-2 positive, 17 controls) underwent bronchoalveolar lavage (BAL) and plasma analysis to assess inflammatory markers using a multiplex assay. SARS-CoV-2 patients showed distinct clinical and immunological features, including prolonged ICU stays and elevated markers of systemic inflammation. Cluster analysis revealed subgroup-specific immune signatures, with COVID-19 survivors demonstrating coordinated cytokine/chemokine interactions suggestive of adaptive immune regulation, while non-survivors exhibited dysregulated profiles indicative of maladaptive inflammation. The study underscores the spatial segregation of immune responses, with lung-specific inflammation in BAL contrasting with systemic profiles, highlighting the importance of tissue-targeted monitoring. These findings suggest that immune profiling could inform stratification for tailored immunomodulatory therapies, advancing precision approaches in critical care for severe SARS-CoV-2 infections.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157042"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211095","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}
Inflammation plays a crucial role in the pathogenesis of Hodgkin lymphoma. IL-18 is a proinflammatory cytokine. Therefore, we investigated the serum IL-18 levels and their prognostic significance in Hodgkin lymphoma patients.
Method
Serum IL-18 levels were compared between 30 newly diagnosed Hodgkin lymphoma patients and 30 healthy controls. The association between IL-18 levels, clinical findings, prognostic markers, and treatment response was also evaluated in Hodgkin lymphoma patients.
Results
The HL group's IL-18 level (29.28 ± 13.48 pg/mL) was significantly higher than that of the control group (16.69 ± 9.33 pg/mL) (p < 0.001). Significant associations were observed between IL-18 levels and extranodal involvement, B symptom presence, performance status, Ann-Arbor stage, bulky mass presence, bone marrow involvement, and treatment response in Hodgkin lymphoma patients (p = 0.013, p = 0.006, p = 0.009, p = 0.003, p = 0.001, p = 0.02, p = 0.03, respectively). IL-18 levels also positively correlated with LDH and beta-2 microglobulin levels (r = 0.37, p = 0.04, r = 0.5, p = 0.005, respectively).
Conclusion
Serum IL-18 levels are higher in Hodgkin lymphoma patients compared to healthy individuals. IL-18 levels may serve as a prognostic marker and a predictor of treatment response in Hodgkin lymphoma patients.
背景:炎症在霍奇金淋巴瘤的发病机制中起着至关重要的作用。IL-18是一种促炎细胞因子。因此,我们研究了霍奇金淋巴瘤患者血清IL-18水平及其预后意义。方法比较30例新诊断霍奇金淋巴瘤患者与30例健康对照者血清IL-18水平。在霍奇金淋巴瘤患者中,还评估了IL-18水平、临床表现、预后指标和治疗反应之间的关系。结果HL组IL-18水平(29.28±13.48 pg/mL)显著高于对照组(16.69±9.33 pg/mL) (p < 0.001)。在霍奇金淋巴瘤患者中,IL-18水平与结外受损伤、B症状存在、运动状态、an - arbor分期、大块肿块存在、骨髓受损伤和治疗反应之间存在显著相关性(p = 0.013, p = 0.006, p = 0.009, p = 0.003, p = 0.001, p = 0.02, p = 0.03)。IL-18水平与LDH和β -2微球蛋白水平呈正相关(r = 0.37, p = 0.04, r = 0.5, p = 0.005)。结论霍奇金淋巴瘤患者血清IL-18水平高于健康人群。IL-18水平可作为霍奇金淋巴瘤患者治疗反应的预后标志物和预测因子。
{"title":"The significance of serum IL-18 levels in Hodgkin lymphoma patients","authors":"Gülden Sincan , Suat Sincan , Çağrı Kızıltunç , Esra Eğilmez","doi":"10.1016/j.cyto.2025.157044","DOIUrl":"10.1016/j.cyto.2025.157044","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation plays a crucial role in the pathogenesis of Hodgkin lymphoma. IL-18 is a proinflammatory cytokine. Therefore, we investigated the serum IL-18 levels and their prognostic significance in Hodgkin lymphoma patients.</div></div><div><h3>Method</h3><div>Serum IL-18 levels were compared between 30 newly diagnosed Hodgkin lymphoma patients and 30 healthy controls. The association between IL-18 levels, clinical findings, prognostic markers, and treatment response was also evaluated in Hodgkin lymphoma patients.</div></div><div><h3>Results</h3><div>The HL group's IL-18 level (29.28 ± 13.48 pg/mL) was significantly higher than that of the control group (16.69 ± 9.33 pg/mL) (<em>p</em> < 0.001). Significant associations were observed between IL-18 levels and extranodal involvement, B symptom presence, performance status, Ann-Arbor stage, bulky mass presence, bone marrow involvement, and treatment response in Hodgkin lymphoma patients (<em>p</em> = 0.013, <em>p</em> = 0.006, <em>p</em> = 0.009, <em>p</em> = 0.003, <em>p</em> = 0.001, <em>p</em> = 0.02, <em>p</em> = 0.03, respectively). IL-18 levels also positively correlated with LDH and beta-2 microglobulin levels (<em>r</em> = 0.37, <em>p</em> = 0.04, <em>r</em> = 0.5, <em>p</em> = 0.005, respectively).</div></div><div><h3>Conclusion</h3><div>Serum IL-18 levels are higher in Hodgkin lymphoma patients compared to healthy individuals. IL-18 levels may serve as a prognostic marker and a predictor of treatment response in Hodgkin lymphoma patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157044"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218249","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: 2025-10-14DOI: 10.1016/j.cyto.2025.157055
Fatih Serdar Baykal , Serdar Can Güven , Ahmet Kor , Funda Eren , Salim Neşelioğlu , Bünyamin Polat , Serdar Esmer , Berkan Armağan , Kevser Orhan , İsmail Doğan , Yüksel Maraş , Salih Başer , Özcan Erel , Şükran Erten
Aim of this study was to evaluate plasma netrin-1 levels in axial spondyloarthritis and to investigate relations between disease activity and other parameters. Axial spondyloarthritis is a term defining a form of the spondyloarthritis in which axial skeleton is predominantly affected. Netrin-1 is a laminin-like matrix protein belonging to the axonal guide protein family, controlling neuronal migration in the embryonic period and inhibiting leukocyte aggregation to provide neuronal protection in the tissue. Study was conducted cross-sectional. Patients with axial spondyloarthritis between ages of 18–65 who applied to our outpatient clinic were enrolled upon consent. A control group was formed by healthy volunteers. Demographics, clinic, laboratory, imaging data and disease activity scores were recorded. Spondyloarthritis patients were subgrouped as ankylosing spondylitis and non-radiographic axial spondyloarthritis. Serum netrin-1 was measured by a commercial kit in patient and control groups. A total of 60 spondyloarthritis patients and 56 healthy controls were enrolled. No significant differences in serum netrin-1 levels were observed among patient groups and controls. Netrin-1 levels had a significant positive correlation with disease activity parameters and found to be higher in patients with higher disease activity. Receiver operating curve analyses revealed fair discriminative power for active disease. Our results suggest a utility for netrin-1 as a novel biomarker for detecting disease activity in spondyloarthritis, for the first time to the best of our knowledge.
{"title":"The relationship of plasma netrin-1 level with disease activity and other parameters in patients with axial spondyloarthritis","authors":"Fatih Serdar Baykal , Serdar Can Güven , Ahmet Kor , Funda Eren , Salim Neşelioğlu , Bünyamin Polat , Serdar Esmer , Berkan Armağan , Kevser Orhan , İsmail Doğan , Yüksel Maraş , Salih Başer , Özcan Erel , Şükran Erten","doi":"10.1016/j.cyto.2025.157055","DOIUrl":"10.1016/j.cyto.2025.157055","url":null,"abstract":"<div><div>Aim of this study was to evaluate plasma netrin-1 levels in axial spondyloarthritis and to investigate relations between disease activity and other parameters. Axial spondyloarthritis is a term defining a form of the spondyloarthritis in which axial skeleton is predominantly affected. Netrin-1 is a laminin-like matrix protein belonging to the axonal guide protein family, controlling neuronal migration in the embryonic period and inhibiting leukocyte aggregation to provide neuronal protection in the tissue. Study was conducted cross-sectional<strong>.</strong> Patients with axial spondyloarthritis between ages of 18–65 who applied to our outpatient clinic were enrolled upon consent. A control group was formed by healthy volunteers. Demographics, clinic, laboratory, imaging data and disease activity scores were recorded. Spondyloarthritis patients were subgrouped as ankylosing spondylitis and non-radiographic axial spondyloarthritis. Serum netrin-1 was measured by a commercial kit in patient and control groups. A total of 60 spondyloarthritis patients and 56 healthy controls were enrolled. No significant differences in serum netrin-1 levels were observed among patient groups and controls. Netrin-1 levels had a significant positive correlation with disease activity parameters and found to be higher in patients with higher disease activity. Receiver operating curve analyses revealed fair discriminative power for active disease. Our results suggest a utility for netrin-1 as a novel biomarker for detecting disease activity in spondyloarthritis, for the first time to the best of our knowledge.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157055"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297812","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: 2025-11-01DOI: 10.1016/j.cyto.2025.157064
Jessica Cusato , Gian Paolo Caviglia , Alfredo Santovito , Gabriele Ascani , Alessandra Manca , Marta Vernero , Angelo Armandi , Eleonora Dileo , Miriam Antonucci , Maria Alessandra Pavan , Antonio D'Avolio , Davide Giuseppe Ribaldone
Perianal Crohn's disease (pCD) is a debilitating complication of Crohn's disease (CD), affecting approximately 20 % of patients. Genetic polymorphisms in cytokine-related and intracellular signaling pathway genes may influence pCD development, yet data on their role remain limited.
To evaluate the association between specific single nucleotide polymorphisms (SNPs) in cytokine (TNF, IL-6, IL-10, TGF-β) and MAPK pathway-related genes (RAS, RAF-1, ERK) and the pCD development.
This retrospective study included 204 CD patients from a single center, of whom 34 had documented pCD. Clinical, phenotypic, and treatment data were collected. Genotyping was performed by real-time PCR and ARMS-PCR.
IL-6 -597 GG genotype was significantly associated with a reduced risk of pCD (p = 0.049). TNF rs1800629–308 GA genotype showed a trend toward protection (p = 0.07). IL-10 -1082 AA genotype showed a non-significant trend toward increased risk (p = 0.07). No significant associations were found for TGF-β or MAPK-related polymorphisms.
Our findings suggest that polymorphisms in cytokine genes, particularly IL-6 and TNF, may influence the risk of developing perianal complications in CD. These preliminary results warrant validation in larger cohorts to assess their potential as predictive biomarkers for personalized management of pCD.
{"title":"IL-6 and TNF variants as potential determinants of perianal disease in Crohn's patients: a pilot study","authors":"Jessica Cusato , Gian Paolo Caviglia , Alfredo Santovito , Gabriele Ascani , Alessandra Manca , Marta Vernero , Angelo Armandi , Eleonora Dileo , Miriam Antonucci , Maria Alessandra Pavan , Antonio D'Avolio , Davide Giuseppe Ribaldone","doi":"10.1016/j.cyto.2025.157064","DOIUrl":"10.1016/j.cyto.2025.157064","url":null,"abstract":"<div><div>Perianal Crohn's disease (pCD) is a debilitating complication of Crohn's disease (CD), affecting approximately 20 % of patients. Genetic polymorphisms in cytokine-related and intracellular signaling pathway genes may influence pCD development, yet data on their role remain limited.</div><div>To evaluate the association between specific single nucleotide polymorphisms (SNPs) in cytokine (TNF, IL-6, IL-10, TGF-β) and MAPK pathway-related genes (RAS, RAF-1, ERK) and the pCD development.</div><div>This retrospective study included 204 CD patients from a single center, of whom 34 had documented pCD. Clinical, phenotypic, and treatment data were collected. Genotyping was performed by real-time PCR and ARMS-PCR.</div><div><em>IL-6</em> -597 GG genotype was significantly associated with a reduced risk of pCD (<em>p</em> = 0.049). <em>TNF</em> rs1800629–308 GA genotype showed a trend toward protection (<em>p</em> = 0.07). <em>IL-10</em> -1082 AA genotype showed a non-significant trend toward increased risk (p = 0.07). No significant associations were found for TGF-β or MAPK-related polymorphisms.</div><div>Our findings suggest that polymorphisms in cytokine genes, particularly IL-6 and TNF, may influence the risk of developing perianal complications in CD. These preliminary results warrant validation in larger cohorts to assess their potential as predictive biomarkers for personalized management of pCD.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157064"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145413023","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: 2025-11-01DOI: 10.1016/j.cyto.2025.157060
Yanshan Liu , Tuo Xu , Yeting Zhang , Mali Fang
Aims
Explore the expression of miR-503-5p in sepsis and its influence on the inflammatory response.
Methods
A total of 120 patients with sepsis were retrospectively selected as the research subjects, and 80 healthy individuals were simultaneously selected as the control group. Reverse transcription quantitative polymerase chain reaction was used to detect the expression of miR-503-5p and related genes. Pearson correlation analysis was used to determine the relationships between variables, and multivariate logistic regression analysis was applied to analyze the risk factors associated with sepsis. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of serum miR-503-5p levels for sepsis. Sepsis-model cells were created in vitro for the purpose of exploring the possible action mechanism of miR-503-5p in the context of sepsis.
Results
The expression of miR-503-5p in the serum of patients with sepsis is significantly upregulated, and it is positively correlated with the severity of the patients' condition and inflammatory indexes. miR-503-5p has a good diagnostic potential in sepsis. Furthermore, miR-503-5p exhibited a notable increase in expression within lipopolysaccharide (LPS)-stimulated THP-1 cells, which facilitated the inflammatory process. Mechanistically, miR-503-5p exacerbates the inflammatory response in sepsis via targeted suppression of peroxisome proliferator-activated receptor alpha (PPARA).
Conclusions
During sepsis, miR-503-5p shows elevated expression, and it facilitates the inflammatory response through the targeted suppression of PPARA.
{"title":"Clinical value and pro-inflammatory mechanism of miR-503-5p as a novel diagnostic biomarker for Sepsis","authors":"Yanshan Liu , Tuo Xu , Yeting Zhang , Mali Fang","doi":"10.1016/j.cyto.2025.157060","DOIUrl":"10.1016/j.cyto.2025.157060","url":null,"abstract":"<div><h3>Aims</h3><div>Explore the expression of miR-503-5p in sepsis and its influence on the inflammatory response.</div></div><div><h3>Methods</h3><div>A total of 120 patients with sepsis were retrospectively selected as the research subjects, and 80 healthy individuals were simultaneously selected as the control group. Reverse transcription quantitative polymerase chain reaction was used to detect the expression of miR-503-5p and related genes. Pearson correlation analysis was used to determine the relationships between variables, and multivariate logistic regression analysis was applied to analyze the risk factors associated with sepsis. Receiver operating characteristic curve analysis was performed to assess the diagnostic efficacy of serum miR-503-5p levels for sepsis. Sepsis-model cells were created in vitro for the purpose of exploring the possible action mechanism of miR-503-5p in the context of sepsis.</div></div><div><h3>Results</h3><div>The expression of miR-503-5p in the serum of patients with sepsis is significantly upregulated, and it is positively correlated with the severity of the patients' condition and inflammatory indexes. miR-503-5p has a good diagnostic potential in sepsis. Furthermore, miR-503-5p exhibited a notable increase in expression within lipopolysaccharide (LPS)-stimulated THP-1 cells, which facilitated the inflammatory process. Mechanistically, miR-503-5p exacerbates the inflammatory response in sepsis via targeted suppression of peroxisome proliferator-activated receptor alpha (PPARA).</div></div><div><h3>Conclusions</h3><div>During sepsis, miR-503-5p shows elevated expression, and it facilitates the inflammatory response through the targeted suppression of PPARA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157060"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145413024","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}
Cytokines are increasingly incorporated in psychiatric research. While biobanking provides advantages for different study designs, long-term storage could degrade cytokine quality and introduce bias. To date, reports on cytokine stability are based on small sample sizes (n < 20) and do not address long-term (4+ years) storage effects. This article reports two studies evaluating IL-6 and TNF-α measurements in human plasma samples biobanked for long periods. In the first study, with samples stored between 5 and 139 months (11.6 years), IL-6 concentrations were not significantly correlated with storage length in all available baseline data of the Signature Biobank (n[IL-6] = 1206, n[TNF-α] = 1223). TNF-α correlated negatively with storage length (r = −0.217; p < 0.001) indicating a decrease of concentrations with longer storage. In the second study, IL-6 and TNF-α concentrations were measured twice in the same plasma samples of 50 psychiatric participants from the Signature Biobank stored between analyses from 32 to 45 months. We assessed if storage effects differed between analytes. In IL-6, we observe a relatively good stability in samples stored up to 6 years. For TNF-α, we observed only a moderate stability of measurements (rTNF-α = 0.59; rIL-6 = 0.71) with linear decrease over time. As a potential solution, a corrective equation extracted from Study 1 was applied to TNF-α in the Study 2 sample; however, this did not improve correlation coefficients but might be useful in other settings. Integrating samples' age in statistical analyses and/or more systematic quality controls could mitigate degradation process.
{"title":"Long-term storage stability of plasma TNF-α and IL-6 concentrations of psychiatric emergency patients: The Signature Biobank","authors":"Enzo Cipriani , Charles-Édouard Giguère , Cécile Le Page , Helen Findlay , Janick Boissoneault , Stéphane Potvin , Robert-Paul Juster","doi":"10.1016/j.cyto.2025.157033","DOIUrl":"10.1016/j.cyto.2025.157033","url":null,"abstract":"<div><div>Cytokines are increasingly incorporated in psychiatric research. While biobanking provides advantages for different study designs, long-term storage could degrade cytokine quality and introduce bias. To date, reports on cytokine stability are based on small sample sizes (<em>n</em> < 20) and do not address long-term (4+ years) storage effects. This article reports two studies evaluating IL-6 and TNF-α measurements in human plasma samples biobanked for long periods. In the first study, with samples stored between 5 and 139 months (11.6 years), IL-6 concentrations were not significantly correlated with storage length in all available baseline data of the Signature Biobank (n[IL-6] = 1206, n[TNF-α] = 1223). TNF-α correlated negatively with storage length (<em>r</em> = −0.217; <em>p</em> < 0.001) indicating a decrease of concentrations with longer storage. In the second study, IL-6 and TNF-α concentrations were measured twice in the same plasma samples of 50 psychiatric participants from the Signature Biobank stored between analyses from 32 to 45 months. We assessed if storage effects differed between analytes. In IL-6, we observe a relatively good stability in samples stored up to 6 years. For TNF-α, we observed only a moderate stability of measurements (rTNF-α = 0.59; rIL-6 = 0.71) with linear decrease over time. As a potential solution, a corrective equation extracted from Study 1 was applied to TNF-α in the Study 2 sample; however, this did not improve correlation coefficients but might be useful in other settings. Integrating samples' age in statistical analyses and/or more systematic quality controls could mitigate degradation process.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"196 ","pages":"Article 157033"},"PeriodicalIF":3.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249116","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}