Pub Date : 2025-02-01DOI: 10.1016/j.cyto.2024.156834
Rehab G. Khalil , Dina A. Mohammed , Hadeer M. Hamdalla , Osama M. Ahmed
T lymphocytes are among the immunological cells that make up the tumor microenvironment (TME), and they are essential in the growth of tumors and anti-tumor reactions. Regulatory T cells (Treg cells) are a subset of CD4+ T cells in the immune system that suppress the immune system. They are distinguished by their expression of the master transcription factor forkhead box protein P3 (FOXP3). Furthermore, Treg cells are essential for maintaining immunological homeostasis, inhibiting inflammation, and maintaining self-tolerance. In a variety of malignancies within the TME, Treg cells demonstrate notable flexibility and functional diversity. Highly plastic Treg cells can change into Th-like Treg cells in specific circumstances, which allow them to secrete particular pro-inflammatory cytokines. Interleukin 35 (IL-35) is a part of the immunosuppressive cytokines that belong to the IL-12 family. Treg cells release IL-35, which was elevated in the peripheral blood and TME of numerous cancer patients, implying that IL-35 in the TME may be an intriguing target for cancer therapy. In cancer, IL-35 is a two-edged sword; it promotes tumorigenicity in cancer cells while shielding them from apoptosis. Nonetheless, other investigations have mentioned its conflicting effects on cancer prevention. Herein, we provide an updated understanding of the critical mechanisms behind the anticancer immunity mediated by Treg cells plasticity, the role of IL-35, and tactics to strengthen the immune response against malignancies, outlining major clinical trials that used Treg cells/IL-35 therapies in the three main cancer types (lung, breast, and colorectal cancers).
{"title":"The possible anti-tumor effects of regulatory T cells plasticity / IL-35 in the tumor microenvironment of the major three cancer types","authors":"Rehab G. Khalil , Dina A. Mohammed , Hadeer M. Hamdalla , Osama M. Ahmed","doi":"10.1016/j.cyto.2024.156834","DOIUrl":"10.1016/j.cyto.2024.156834","url":null,"abstract":"<div><div>T lymphocytes are among the immunological cells that make up the tumor microenvironment (TME), and they are essential in the growth of tumors and anti-tumor reactions. Regulatory T cells (Treg cells) are a subset of CD4+ T cells in the immune system that suppress the immune system. They are distinguished by their expression of the master transcription factor forkhead box protein P3 (FOXP3). Furthermore, Treg cells are essential for maintaining immunological homeostasis, inhibiting inflammation, and maintaining self-tolerance. In a variety of malignancies within the TME, Treg cells demonstrate notable flexibility and functional diversity. Highly plastic Treg cells can change into Th-like Treg cells in specific circumstances, which allow them to secrete particular pro-inflammatory cytokines. Interleukin 35 (IL-35) is a part of the immunosuppressive cytokines that belong to the IL-12 family. Treg cells release IL-35, which was elevated in the peripheral blood and TME of numerous cancer patients, implying that IL-35 in the TME may be an intriguing target for cancer therapy. In cancer, IL-35 is a two-edged sword; it promotes tumorigenicity in cancer cells while shielding them from apoptosis. Nonetheless, other investigations have mentioned its conflicting effects on cancer prevention. Herein, we provide an updated understanding of the critical mechanisms behind the anticancer immunity mediated by Treg cells plasticity, the role of IL-35, and tactics to strengthen the immune response against malignancies, outlining major clinical trials that used Treg cells/IL-35 therapies in the three main cancer types (lung, breast, and colorectal cancers).</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156834"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851834","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156835
Wenya Cai , Qingshan Yan , Yuhong Deng , Yong Guo
Objective
Based on current evidence suggesting that bisphenol A (BPA) may contribute to obesity through the modulation of inflammatory markers, this study aims to investigate the correlation between BPA exposure and cellular inflammatory factors in preschool children.
Methods
A total of 155 preschool children aged 4–6 years were included. Urine and blood samples were collected. BPA exposure was detected by liquid chromatography-tandem mass spectrometry through urine samples. The levels of six inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were determined by flow fluorescence technique. The correlation between urinary BPA exposure and cellular inflammatory factors was analyzed using Spearman's correlation and respectively stratified by gender and BMI.
Results
The detection rate of BPA in urine samples was 100 %. The median urinary BPA concentration was 0.48 μg/L(IQR:0.25–1.02 μg/L), and the creatinine-adjusted BPA concentration was 0.94 μg/g(IQR:0.57–1.66 μg/g). BPA level was negatively correlated with IL-10 (r = −0.172, P < 0.05). After stratification by gender, the negative association between BPA exposure and IL-10 was found in females (r = −0.257, P < 0.05), while no association was found in males. According to BMI stratification, BPA exposure in overweight/obese children was positively correlated with IL-6 (r = 0.354, P < 0.05).
Conclusions
Our study demonstrated that BPA exposure in preschool children was correlated with a decrease in levels of IL-10, and this effect was significantly expressed in girls. In addition, BPA exposure in overweight/obese children was correlated with increased levels of IL-6. However, the mechanism between BPA and inflammatory factors remains to be further explored.
{"title":"The correlation of bisphenol A exposure on inflammatory cytokines in preschool children","authors":"Wenya Cai , Qingshan Yan , Yuhong Deng , Yong Guo","doi":"10.1016/j.cyto.2024.156835","DOIUrl":"10.1016/j.cyto.2024.156835","url":null,"abstract":"<div><h3>Objective</h3><div>Based on current evidence suggesting that bisphenol A (BPA) may contribute to obesity through the modulation of inflammatory markers, this study aims to investigate the correlation between BPA exposure and cellular inflammatory factors in preschool children.</div></div><div><h3>Methods</h3><div>A total of 155 preschool children aged 4–6 years were included. Urine and blood samples were collected. BPA exposure was detected by liquid chromatography-tandem mass spectrometry through urine samples. The levels of six inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were determined by flow fluorescence technique. The correlation between urinary BPA exposure and cellular inflammatory factors was analyzed using Spearman's correlation and respectively stratified by gender and BMI.</div></div><div><h3>Results</h3><div>The detection rate of BPA in urine samples was 100 %. The median urinary BPA concentration was 0.48 μg/L(IQR:0.25–1.02 μg/L), and the creatinine-adjusted BPA concentration was 0.94 μg/g(IQR:0.57–1.66 μg/g). BPA level was negatively correlated with IL-10 (<em>r</em> = −0.172, <em>P</em> < 0.05). After stratification by gender, the negative association between BPA exposure and IL-10 was found in females (<em>r</em> = −0.257, <em>P</em> < 0.05), while no association was found in males. According to BMI stratification, BPA exposure in overweight/obese children was positively correlated with IL-6 (<em>r</em> = 0.354, <em>P</em> < 0.05).</div></div><div><h3>Conclusions</h3><div>Our study demonstrated that BPA exposure in preschool children was correlated with a decrease in levels of IL-10, and this effect was significantly expressed in girls. In addition, BPA exposure in overweight/obese children was correlated with increased levels of IL-6. However, the mechanism between BPA and inflammatory factors remains to be further explored.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156835"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845449","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156842
K. Matsuda , Y. Ota , H. Uemachi , R. Taoda , Y. Tsunashima , H. Ban , Y. Nagai
Toll-like receptors (TLRs) are crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. Because of their strong immunostimulatory activity, TLRs are thought to be a “double-edged sword” for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509. We have demonstrated that the anti-tumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. In this study, we compared the anti-tumor effects of EIK1001 and 5DEX-0509R, and analyzed its unique immune reaction against tumors to evaluate whether 5DEX-0509R is suitable for further clinical study. 5DEX-0509R showed superior anti-tumor activity compared to EIK1001, an R848 sulfate currently in phase 2 trials, with comparable systemic cytokine profiles. 5DEX-0509R elicited unique CD4 T cell and B cell-dependent anti-tumor effects. We also found that 5DEX-0509R synergistically suppresses tumors with oxaliplatin by changing M2 macrophages that cause oxaliplatin to become resistant to antitumor M1 macrophages. In addition, 5DEX-0509R caused a rapid but not sustained cytokine elevation in both rats and dogs. We believe 5DEX-0509R is worth pursuing for clinical trials.
{"title":"Examination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine","authors":"K. Matsuda , Y. Ota , H. Uemachi , R. Taoda , Y. Tsunashima , H. Ban , Y. Nagai","doi":"10.1016/j.cyto.2024.156842","DOIUrl":"10.1016/j.cyto.2024.156842","url":null,"abstract":"<div><div>Toll-like receptors (TLRs) are crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. Because of their strong immunostimulatory activity, TLRs are thought to be a “double-edged sword” for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activator conjugate (D-TAC) technology which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509. We have demonstrated that the anti-tumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. In this study, we compared the anti-tumor effects of EIK1001 and 5DEX-0509R, and analyzed its unique immune reaction against tumors to evaluate whether 5DEX-0509R is suitable for further clinical study. 5DEX-0509R showed superior anti-tumor activity compared to EIK1001, an R848 sulfate currently in phase 2 trials, with comparable systemic cytokine profiles. 5DEX-0509R elicited unique CD4 T cell and B cell-dependent anti-tumor effects. We also found that 5DEX-0509R synergistically suppresses tumors with oxaliplatin by changing M2 macrophages that cause oxaliplatin to become resistant to antitumor M1 macrophages. In addition, 5DEX-0509R caused a rapid but not sustained cytokine elevation in both rats and dogs. We believe 5DEX-0509R is worth pursuing for clinical trials.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156842"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890867","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156844
Hong-Zhe Zhu , Yan Niu , Jian-Xun Wen , Cheng Yan , Su-Na Cha , Yue Gao , Xu-Lei Hao , Wen-Jie Hou , Li Yan , Ting-Wang Jiang , Zhi-De Hu , Wen-Qi Zheng
Background
Tuberculous pleural effusion (TPE) diagnosis still faces many difficulties and challenges. Some studies have shown that pleural interleukin −27 (IL-27) had a diagnostic potential for TPE. However, their findings are not always consistent. This study aimed to investigate the diagnostic accuracy of pleural IL-27 for TPE.
Methods
We prospectively enrolled 211 patients with undiagnosed pleural effusion. Effusion Mycobacterium tuberculosis (Mtb) culture, Ziehl-Neelsen staining, biopsy, and response to antituberculosis therapy were used to define TPE. The pleural IL-27 levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic curve (ROC) with the area under the curve (AUC) was used to evaluate the diagnostic accuracy of IL-27 for TPE. In addition, we investigated the influence of age on the diagnostic performance of IL-27 by resampling patients with different upper age limits in the inclusion criteria.
Results
Among the 211 enrolled participants, 33 were TPE and 178 were non-TPE. The mean concentration of IL-27 in TPE patients was significantly higher than that of non-TPE patients. The AUC of IL-27 was 0.76 (95 %CI: 0.67–0.86). At the threshold of 500 pg/mL, the sensitivity and specificity of IL-27 were 0.26 (95 %CI: 0.20–0.33) and 0.91 (95 %CI:0.76–0.97), respectively. The AUC of IL-27 is 0.84 in patients with an upper age limit of 70. Still, it decreased to 0.76 in patients with an upper age limit of 75.
Conclusion
Age can affect the diagnostic performance of IL-27 for TPE.
{"title":"Accuracy of interleukin-27 in diagnosing tuberculous pleural effusion: Age should be considered","authors":"Hong-Zhe Zhu , Yan Niu , Jian-Xun Wen , Cheng Yan , Su-Na Cha , Yue Gao , Xu-Lei Hao , Wen-Jie Hou , Li Yan , Ting-Wang Jiang , Zhi-De Hu , Wen-Qi Zheng","doi":"10.1016/j.cyto.2024.156844","DOIUrl":"10.1016/j.cyto.2024.156844","url":null,"abstract":"<div><h3>Background</h3><div>Tuberculous pleural effusion (TPE) diagnosis still faces many difficulties and challenges. Some studies have shown that pleural interleukin −27 (IL-27) had a diagnostic potential for TPE. However, their findings are not always consistent. This study aimed to investigate the diagnostic accuracy of pleural IL-27 for TPE.</div></div><div><h3>Methods</h3><div>We prospectively enrolled 211 patients with undiagnosed pleural effusion. Effusion <em>Mycobacterium tuberculosis (Mtb)</em> culture, Ziehl-Neelsen staining, biopsy, and response to antituberculosis therapy were used to define TPE. The pleural IL-27 levels were determined by enzyme-linked immunosorbent assay (ELISA). A receiver operating characteristic curve (ROC) with the area under the curve (AUC) was used to evaluate the diagnostic accuracy of IL-27 for TPE. In addition, we investigated the influence of age on the diagnostic performance of IL-27 by resampling patients with different upper age limits in the inclusion criteria.</div></div><div><h3>Results</h3><div>Among the 211 enrolled participants, 33 were TPE and 178 were non-TPE. The mean concentration of IL-27 in TPE patients was significantly higher than that of non-TPE patients. The AUC of IL-27 was 0.76 (95 %CI: 0.67–0.86). At the threshold of 500 pg/mL, the sensitivity and specificity of IL-27 were 0.26 (95 %CI: 0.20–0.33) and 0.91 (95 %CI:0.76–0.97), respectively. The AUC of IL-27 is 0.84 in patients with an upper age limit of 70. Still, it decreased to 0.76 in patients with an upper age limit of 75.</div></div><div><h3>Conclusion</h3><div>Age can affect the diagnostic performance of IL-27 for TPE.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156844"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913236","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156849
Jiaqi Kong , Xinpeng Liu , Huishu Li , Chubo Yang , Tao Jiang , Ying Yan , Nan Miao , Sen Mu , Yuanbo Zhan
Introduction
Behcet's syndrome, as a vasculitic disease involving multiple systems, often induces oral mucosal ulcers. However, levels of inflammatory cytokines and metabolites are unknown for the probability of developing the disease. This study aims to reveal the causal relationship between the cytokines and metabolites and Behcet's syndrome through Mendelian randomization analysis.
Materials and methods
The instrumental variable single nucleotide polymorphisms (SNPs) were used in the study, which showed associations between 91 cytokines and 553 metabolites, respectively. To explore the causal relationship between these exposure factors and Behcet's syndrome, the random effects inverse variance weighting method was adopted. In addition, sensitivity analysis was carried out using Cochran's Q test, heterogeneity test, horizontal pleotropy test and MR-Egger intercept test to evaluate the robustness and validity of our research results.
Results
A total of five substances were identified as causally related to Behcet's syndrome, namely, the cellular factors Interleukin 12 subunit beta(IL-12B) and Interleukin-33(IL-33), the metabolite mannitol, X-12728, and Ratio of Bisallylic groups to double bonds. Furthermore, no significant evidence suggesting heterogeneity or pleiotropy was observed.
Conclusion
Our study adds to current knowledge on the role of specific inflammatory cytokines and metabolites in aetiology of Behcet's syndrome. The identified cytokines and metabolites might be used as markers for clinical screening and prevention of Behcet's syndrome, as well as candidate molecules for future mechanism exploration and drug target selection. Further validation is needed to assess the potential of these cytokines and metabolites as pharmacological targets for Behcet's syndrome prevention.
{"title":"Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization","authors":"Jiaqi Kong , Xinpeng Liu , Huishu Li , Chubo Yang , Tao Jiang , Ying Yan , Nan Miao , Sen Mu , Yuanbo Zhan","doi":"10.1016/j.cyto.2024.156849","DOIUrl":"10.1016/j.cyto.2024.156849","url":null,"abstract":"<div><h3>Introduction</h3><div>Behcet's syndrome, as a vasculitic disease involving multiple systems, often induces oral mucosal ulcers. However, levels of inflammatory cytokines and metabolites are unknown for the probability of developing the disease. This study aims to reveal the causal relationship between the cytokines and metabolites and Behcet's syndrome through Mendelian randomization analysis.</div></div><div><h3>Materials and methods</h3><div>The instrumental variable single nucleotide polymorphisms (SNPs) were used in the study, which showed associations between 91 cytokines and 553 metabolites, respectively. To explore the causal relationship between these exposure factors and Behcet's syndrome, the random effects inverse variance weighting method was adopted. In addition, sensitivity analysis was carried out using Cochran's Q test, heterogeneity test, horizontal pleotropy test and MR-Egger intercept test to evaluate the robustness and validity of our research results.</div></div><div><h3>Results</h3><div>A total of five substances were identified as causally related to Behcet's syndrome, namely, the cellular factors Interleukin 12 subunit beta(IL-12B) and Interleukin-33(IL-33), the metabolite mannitol, X-12728, and Ratio of Bisallylic groups to double bonds. Furthermore, no significant evidence suggesting heterogeneity or pleiotropy was observed.</div></div><div><h3>Conclusion</h3><div>Our study adds to current knowledge on the role of specific inflammatory cytokines and metabolites in aetiology of Behcet's syndrome. The identified cytokines and metabolites might be used as markers for clinical screening and prevention of Behcet's syndrome, as well as candidate molecules for future mechanism exploration and drug target selection. Further validation is needed to assess the potential of these cytokines and metabolites as pharmacological targets for Behcet's syndrome prevention.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156849"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930003","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156847
Yang Han , Delong Wang , Qian Wang , Ying Liu , Mingzhe Yan , Fuli Ren , Xujuan Hu , Rui Gong , Huadong Li , Jingwen He , Yaling Jia , Jun Wan , Gangyu Long , Kaidi Nan , Chaolin Huang , Congrui Xu , Qun Yao , Dingyu Zhang
In the post-pandemic era, research on respiratory diseases should refocus on pathogens other than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory pathogens, highly infectious to children, with to different modes of infection, such as single-pathogen infections and co-infections. Understanding the seasonal patterns of these pathogens, alongside identifying single infections and co-infections and their impact on the pediatric immune status, is crucial for clinical diagnosis, treatment, and prognosis in children. Our study found that from December 2023 to April 2024, the main co-infection combinations in children shifted from Mycoplasma pneumonia and influenza virus A (MP + IVA) to Bordetella pertussis and rhinovirus (BP + RhV). To explore the impact of these infections, two cohorts were established to analyze the effects of single and co-infections of four respiratory pathogens, MP, IVA, BP, and RhV, on the immune status of pediatric patients. Using multi-cytokine analysis, cytokines, such as PDGF-BB, that were differentially expressed between patients with single and co-infections were identified. Additionally, we observed that children with single-pathogen infections generally exhibited more severe conditions, as evidenced by higher overall cytokine expression than those with co-infections. Our findings provide an important theoretical basis for understanding the pathogenic mechanisms of single and co-infections of respiratory pathogens and clinically differentiating pediatric patients with various respiratory infections.
{"title":"Seasonal shifts in respiratory pathogen co-infections and the associated differential induction of cytokines in children","authors":"Yang Han , Delong Wang , Qian Wang , Ying Liu , Mingzhe Yan , Fuli Ren , Xujuan Hu , Rui Gong , Huadong Li , Jingwen He , Yaling Jia , Jun Wan , Gangyu Long , Kaidi Nan , Chaolin Huang , Congrui Xu , Qun Yao , Dingyu Zhang","doi":"10.1016/j.cyto.2024.156847","DOIUrl":"10.1016/j.cyto.2024.156847","url":null,"abstract":"<div><div>In the post-pandemic era, research on respiratory diseases should refocus on pathogens other than the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory pathogens, highly infectious to children, with to different modes of infection, such as single-pathogen infections and co-infections. Understanding the seasonal patterns of these pathogens, alongside identifying single infections and co-infections and their impact on the pediatric immune status, is crucial for clinical diagnosis, treatment, and prognosis in children. Our study found that from December 2023 to April 2024, the main co-infection combinations in children shifted from <em>Mycoplasma pneumonia</em> and influenza virus A (MP + IVA) to <em>Bordetella pertussis</em> and rhinovirus (BP + RhV). To explore the impact of these infections, two cohorts were established to analyze the effects of single and co-infections of four respiratory pathogens, MP, IVA, BP, and RhV, on the immune status of pediatric patients. Using multi-cytokine analysis, cytokines, such as PDGF-BB, that were differentially expressed between patients with single and co-infections were identified. Additionally, we observed that children with single-pathogen infections generally exhibited more severe conditions, as evidenced by higher overall cytokine expression than those with co-infections. Our findings provide an important theoretical basis for understanding the pathogenic mechanisms of single and co-infections of respiratory pathogens and clinically differentiating pediatric patients with various respiratory infections.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156847"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890870","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 : 2025-02-01DOI: 10.1016/j.cyto.2025.156864
Jing Fan , Yu-chi Zhang , Dao-feng Zheng , Mu Zhang , Hang Liu , Miao He , Zhong-jun Wu
{"title":"Corrigendum to “IL-27 is elevated in sepsis with acute hepatic injury and promotes hepatic damage and inflammation in the CLP model” [Cytokine 127 (2020) 154936]","authors":"Jing Fan , Yu-chi Zhang , Dao-feng Zheng , Mu Zhang , Hang Liu , Miao He , Zhong-jun Wu","doi":"10.1016/j.cyto.2025.156864","DOIUrl":"10.1016/j.cyto.2025.156864","url":null,"abstract":"","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156864"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The COVID-19 pandemic has caused significant morbidity and mortality worldwide. The emergence of the Alpha and Delta variants of SARS-CoV-2 has led to a renewed interest in using interferon therapy as a potential treatment option. Interferons are a group of signaling proteins produced by host cells in response to viral infections. They play a critical role in the innate immune response to viral infections by inducing an antiviral state in infected and neighboring cells. Interferon therapy has shown promise as a potential treatment option for COVID-19. In this review paper, we review the current knowledge regarding interferon therapy in the context of the Alpha and Delta variants of SARS-CoV-2 and discuss the challenges that must be overcome to translate laboratory findings into effective clinical treatments.
{"title":"Interferon therapy in alpha and Delta variants of SARS-CoV-2: The dichotomy between laboratory success and clinical realities","authors":"Atefe Alirezaee , Milad Mirmoghtadaei , Hanieh Heydarlou , Asiye Akbarian , Zahra Alizadeh","doi":"10.1016/j.cyto.2024.156829","DOIUrl":"10.1016/j.cyto.2024.156829","url":null,"abstract":"<div><div>The COVID-19 pandemic has caused significant morbidity and mortality worldwide. The emergence of the Alpha and Delta variants of SARS-CoV-2 has led to a renewed interest in using interferon therapy as a potential treatment option. Interferons are a group of signaling proteins produced by host cells in response to viral infections. They play a critical role in the innate immune response to viral infections by inducing an antiviral state in infected and neighboring cells. Interferon therapy has shown promise as a potential treatment option for COVID-19. In this review paper, we review the current knowledge regarding interferon therapy in the context of the Alpha and Delta variants of SARS-CoV-2 and discuss the challenges that must be overcome to translate laboratory findings into effective clinical treatments.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156829"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851833","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156839
Mariagrazia Palladini , Mario Gennaro Mazza , Rebecca De Lorenzo , Sara Spadini , Veronica Aggio , Margherita Bessi , Federico Calesella , Beatrice Bravi , Patrizia Rovere-Querini , Francesco Benedetti , COVID-19 BioB Outpatient Clinic Study group
Growing evidence suggests the neurobiological mechanism upholding post-COVID-19 depression mainly relates to immune response and subsequent unresolved low-grade inflammation. Herein we exploit a broad panel of cytokines serum levels measured in COVID-19 survivors at one- and three-month since infection to predict post-COVID-19 depression.
87 COVID survivors were screened for depressive symptomatology at one- and three-month after discharge through the Beck Depression Inventory (BDI-13) and the Zung Self-Rating Depression Scale (ZSDS) at San Raffaele Hospital. Blood samples were collected at both timepoints and analyzed through Luminex. We entered one-month 42 inflammatory compounds into two separate penalized logistic regression models to evaluate their reliability in identifying COVID-19 survivors suffering from clinical depression at the two timepoints, applied within a machine learning routine. Delta values of analytes lowering between timepoints were entered in a third model predicting presence long-term depression. 5000 bootstraps were computed to determine significance of predictors.
The cross-sectional model reached a balance accuracy (BA) of 76 % and a sensitivity of 70 %. Post-COVID-19 depression was predicted by high levels of CCL17, CCL22. On the other hand, CXCL10, CCL2, CCL3, CCL8, CXCL5, CCL15, CCL23, CXCL13, and GM-CSF showed protective effects. The longitudinal model obtained good performance as well (BA = 74 % and sensitivity = 68 %), revealing CXCL16 and CCL25 as additional drivers of clinical depression. Moreover, dynamic changes of analytes over time accurately predicted long-term depression (BA = 76 % and sensitivity = 75 %).
Our findings unveil a putative immune profile upholding post-COVID-19 depression, thus reinforcing the need to deepen molecular mechanisms to appropriately target depression.
{"title":"Circulating inflammatory markers predict depressive symptomatology in COVID-19 survivors","authors":"Mariagrazia Palladini , Mario Gennaro Mazza , Rebecca De Lorenzo , Sara Spadini , Veronica Aggio , Margherita Bessi , Federico Calesella , Beatrice Bravi , Patrizia Rovere-Querini , Francesco Benedetti , COVID-19 BioB Outpatient Clinic Study group","doi":"10.1016/j.cyto.2024.156839","DOIUrl":"10.1016/j.cyto.2024.156839","url":null,"abstract":"<div><div>Growing evidence suggests the neurobiological mechanism upholding post-COVID-19 depression mainly relates to immune response and subsequent unresolved low-grade inflammation. Herein we exploit a broad panel of cytokines serum levels measured in COVID-19 survivors at one- and three-month since infection to predict post-COVID-19 depression.</div><div>87 COVID survivors were screened for depressive symptomatology at one- and three-month after discharge through the Beck Depression Inventory (BDI-13) and the Zung Self-Rating Depression Scale (ZSDS) at San Raffaele Hospital. Blood samples were collected at both timepoints and analyzed through Luminex. We entered one-month 42 inflammatory compounds into two separate penalized logistic regression models to evaluate their reliability in identifying COVID-19 survivors suffering from clinical depression at the two timepoints, applied within a machine learning routine. Delta values of analytes lowering between timepoints were entered in a third model predicting presence long-term depression. 5000 bootstraps were computed to determine significance of predictors.</div><div>The cross-sectional model reached a balance accuracy (BA) of 76 % and a sensitivity of 70 %. Post-COVID-19 depression was predicted by high levels of CCL17, CCL22. On the other hand, CXCL10, CCL2, CCL3, CCL8, CXCL5, CCL15, CCL23, CXCL13, and GM-CSF showed protective effects. The longitudinal model obtained good performance as well (BA = 74 % and sensitivity = 68 %), revealing CXCL16 and CCL25 as additional drivers of clinical depression. Moreover, dynamic changes of analytes over time accurately predicted long-term depression (BA = 76 % and sensitivity = 75 %).</div><div>Our findings unveil a putative immune profile upholding post-COVID-19 depression, thus reinforcing the need to deepen molecular mechanisms to appropriately target depression.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156839"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862591","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 : 2025-02-01DOI: 10.1016/j.cyto.2024.156843
Jing-Yu Li , Yan-Jun Ling , Wen-Hui Bao , Wen-Na Zhang , Xin-Miao Han , Xiao-Chen Zheng , Qi Zhao
Background
Based on previous research, it is well-established that myasthenia gravis (MG) is linked to chronic inflammation. However, the exact nature of the relationship between inflammatory factors and the development of MG remains unclear. Consequently, the objective of this study is to explore whether alterations in the levels of inflammatory factors, as influenced by genetic factors, are associated with the occurrence of MG. This will be achieved through a two-sample Mendelian randomization (MR) analysis.
Methods
We conducted a bidirectional Mendelian randomization (MR) study utilizing genetic data from genome-wide association studies (GWAS), encompassing 1873 MG cases and 36,370 individuals of European ancestry as controls. Data on inflammatory cytokines were obtained from GWAS data of 8293, healthy participants. The inverse variance-weighted (IVW) method was primarily employed to investigate the causal relationship between exposure and outcome. Additionally, various sensitivity analysis methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were applied to strengthen the reliability of the results. Through these rigorous approaches, we extensively examined the relationship between inflammatory factors and MG; however, further research is required to establish the specific causal relationship.
Results
After applying Bonferroni correction, the genetic predictions revealed a significant correlation between Monokine induced by gamma interferon (MIG) and MG (OR: 1.09, 95 % CI: 1.04–1.14; P = 0.0006). Furthermore, there were preliminary findings indicating a positive genetic association between Eotaxin and interleukin-2 receptor antagonist (IL-2ra) with MG (OR: 0.81, 95 % CI: 0.66–0.99, P = 0.044; OR: 0.80, 95 % CI: 0.68–0.94, P = 0.008). Reverse MR analysis provided initial evidence of associations between MIP1α, GROa, IL-13, TRAIL, IL-2ra, and IL-1ra with the development of MG. No indications of pleiotropy or heterogeneity among genetic variants were observed (P > 0.05).
Conclusion
This study uncovers a new connection between inflammatory cytokines and MG, shedding light on potential factors contributing to the development of the disease. Elevated levels of Eotaxin and IL-2ra are associated with a higher risk of MG, while indicating that MIG, MIP1α, GROa, IL-13, TRAIL, IL-2ra, and IL-1ra may be elevated as a result of MG, Especially MIG. These findings suggest that targeting and regulating specific inflammatory factors could offer promising avenues for the treatment and prevention of MG.
{"title":"Exploring the causal relationship between inflammatory cytokines and myasthenia gravis: A two-way Mendelian randomization study","authors":"Jing-Yu Li , Yan-Jun Ling , Wen-Hui Bao , Wen-Na Zhang , Xin-Miao Han , Xiao-Chen Zheng , Qi Zhao","doi":"10.1016/j.cyto.2024.156843","DOIUrl":"10.1016/j.cyto.2024.156843","url":null,"abstract":"<div><h3>Background</h3><div>Based on previous research, it is well-established that myasthenia gravis (MG) is linked to chronic inflammation. However, the exact nature of the relationship between inflammatory factors and the development of MG remains unclear. Consequently, the objective of this study is to explore whether alterations in the levels of inflammatory factors, as influenced by genetic factors, are associated with the occurrence of MG. This will be achieved through a two-sample Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>We conducted a bidirectional Mendelian randomization (MR) study utilizing genetic data from genome-wide association studies (GWAS), encompassing 1873 MG cases and 36,370 individuals of European ancestry as controls. Data on inflammatory cytokines were obtained from GWAS data of 8293, healthy participants. The inverse variance-weighted (IVW) method was primarily employed to investigate the causal relationship between exposure and outcome. Additionally, various sensitivity analysis methods such as MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were applied to strengthen the reliability of the results. Through these rigorous approaches, we extensively examined the relationship between inflammatory factors and MG; however, further research is required to establish the specific causal relationship.</div></div><div><h3>Results</h3><div>After applying Bonferroni correction, the genetic predictions revealed a significant correlation between Monokine induced by gamma interferon (MIG) and MG (OR: 1.09, 95 % CI: 1.04–1.14; <em>P</em> = 0.0006). Furthermore, there were preliminary findings indicating a positive genetic association between Eotaxin and interleukin-2 receptor antagonist (IL-2ra) with MG (OR: 0.81, 95 % CI: 0.66–0.99, <em>P</em> = 0.044; OR: 0.80, 95 % CI: 0.68–0.94, <em>P</em> = 0.008). Reverse MR analysis provided initial evidence of associations between MIP1α, GROa, IL-13, TRAIL, IL-2ra, and IL-1ra with the development of MG. No indications of pleiotropy or heterogeneity among genetic variants were observed (<em>P</em> > 0.05).</div></div><div><h3>Conclusion</h3><div>This study uncovers a new connection between inflammatory cytokines and MG, shedding light on potential factors contributing to the development of the disease. Elevated levels of Eotaxin and IL-2ra are associated with a higher risk of MG, while indicating that MIG, MIP1α, GROa, IL-13, TRAIL, IL-2ra, and IL-1ra may be elevated as a result of MG, Especially MIG. These findings suggest that targeting and regulating specific inflammatory factors could offer promising avenues for the treatment and prevention of MG.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"186 ","pages":"Article 156843"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}