首页 > 最新文献

Cytokine最新文献

英文 中文
The possible anti-tumor effects of regulatory T cells plasticity / IL-35 in the tumor microenvironment of the major three cancer types 调节性T细胞可塑性/ IL-35在三种主要肿瘤微环境中可能的抗肿瘤作用
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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).
T淋巴细胞是构成肿瘤微环境(tumor microenvironment, TME)的免疫细胞之一,在肿瘤生长和抗肿瘤反应中起着至关重要的作用。调节性T细胞(Treg细胞)是免疫系统中抑制免疫系统的CD4+ T细胞的一个亚群。它们通过表达主转录因子叉头盒蛋白P3 (FOXP3)来区分。此外,Treg细胞对于维持免疫稳态、抑制炎症和维持自身耐受性至关重要。在TME内的各种恶性肿瘤中,Treg细胞表现出显著的灵活性和功能多样性。高度可塑性的Treg细胞可以在特定环境下转变为th样Treg细胞,这使得它们能够分泌特定的促炎细胞因子。白细胞介素35 (Interleukin 35, IL-35)是免疫抑制细胞因子,属于IL-12家族。Treg细胞释放IL-35, IL-35在许多癌症患者的外周血和TME中升高,这意味着TME中的IL-35可能是癌症治疗的一个有趣的靶点。在癌症中,IL-35是一把双刃剑;它促进癌细胞的致瘤性,同时保护癌细胞免于凋亡。尽管如此,其他研究也提到了它在预防癌症方面的相互矛盾的作用。在此,我们对Treg细胞可塑性介导的抗癌免疫的关键机制、IL-35的作用以及加强恶性肿瘤免疫反应的策略提供了最新的理解,概述了在三种主要癌症类型(肺癌、乳腺癌和结直肠癌)中使用Treg细胞/IL-35治疗的主要临床试验。
{"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 ,&nbsp;Dina A. Mohammed ,&nbsp;Hadeer M. Hamdalla ,&nbsp;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}
引用次数: 0
The correlation of bisphenol A exposure on inflammatory cytokines in preschool children 学龄前儿童双酚A暴露与炎症细胞因子的相关性。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
目的:基于目前的证据表明双酚A (BPA)可能通过调节炎症标志物而导致肥胖,本研究旨在探讨BPA暴露与学龄前儿童细胞炎症因子的相关性。方法:对155名4 ~ 6岁学龄前儿童进行调查。采集了尿液和血液样本。采用液相色谱-串联质谱法对尿液样本进行BPA暴露检测。流式荧光法检测6种炎症因子(IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ)水平。采用Spearman相关分析尿液BPA暴露与细胞炎症因子的相关性,并按性别和BMI分别分层。结果:尿液样本中BPA的检出率为100%。尿中位BPA浓度为0.48 μg/L(IQR:0.25 ~ 1.02 μg/L),肌酐调节的BPA浓度为0.94 μg/g(IQR:0.57 ~ 1.66 μg/g)。BPA水平与IL-10水平呈负相关(r = -0.172, P)。结论:我们的研究表明,学龄前儿童BPA暴露与IL-10水平降低相关,且这种影响在女孩中显著表达。此外,超重/肥胖儿童的BPA暴露与IL-6水平升高有关。然而,双酚a与炎症因子之间的机制仍有待进一步探讨。
{"title":"The correlation of bisphenol A exposure on inflammatory cytokines in preschool children","authors":"Wenya Cai ,&nbsp;Qingshan Yan ,&nbsp;Yuhong Deng ,&nbsp;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> &lt; 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> &lt; 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> &lt; 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}
引用次数: 0
Examination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine 肿瘤巨噬细胞靶向纳米药物5DEX-0509R的潜在临床应用研究
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
toll样受体(TLRs)对于检测感染和激活下游信号通路至关重要,下游信号通路导致促炎细胞因子和干扰素的产生。由于其强大的免疫刺激活性,tlr被认为是全身治疗的“双刃剑”,即使在癌症领域也是如此。为了解决这个问题,我们开发了基于葡聚糖的TAM靶向激活物缀合物(D-TAC)技术,该技术成功地利用肿瘤相关巨噬细胞(TAM)递送TLR7激动剂DSP-0509。我们已经证明,我们的最佳候选药物5DEX-0509R的抗肿瘤作用依赖于tam的丰度,这与它们的作用机制是一致的。本研究通过比较EIK1001与5DEX-0509R的抗肿瘤作用,分析其对肿瘤的独特免疫反应,评价5DEX-0509R是否适合进一步的临床研究。与EIK1001相比,5DEX-0509R显示出更好的抗肿瘤活性,EIK1001是一种R848硫酸盐,目前正在进行2期试验,具有相似的全身细胞因子特征。5DEX-0509R诱导独特的CD4 T细胞和B细胞依赖性抗肿瘤作用。我们还发现5DEX-0509R通过改变M2巨噬细胞,使奥沙利铂对抗肿瘤M1巨噬细胞产生耐药性,从而协同抑制肿瘤与奥沙利铂。此外,5DEX-0509R在大鼠和狗中引起快速但不持续的细胞因子升高。我们认为5DEX-0509R值得进行临床试验。
{"title":"Examination of the potential clinical application of 5DEX-0509R, the tumor macrophage-targeting nanomedicine","authors":"K. Matsuda ,&nbsp;Y. Ota ,&nbsp;H. Uemachi ,&nbsp;R. Taoda ,&nbsp;Y. Tsunashima ,&nbsp;H. Ban ,&nbsp;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}
引用次数: 0
Accuracy of interleukin-27 in diagnosing tuberculous pleural effusion: Age should be considered 白细胞介素-27诊断结核性胸腔积液的准确性:应考虑年龄。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
背景:结核性胸腔积液(TPE)的诊断仍面临许多困难和挑战。一些研究表明,胸膜白介素-27 (IL-27)有诊断TPE的潜力。然而,他们的发现并不总是一致的。本研究旨在探讨胸膜IL-27对TPE的诊断准确性。方法:我们前瞻性地纳入211例未确诊的胸腔积液患者。结核分枝杆菌(Mtb)积液培养、Ziehl-Neelsen染色、活检和对抗结核治疗的反应被用来定义TPE。采用酶联免疫吸附试验(ELISA)检测胸膜IL-27水平。采用受试者工作特征曲线(ROC)和曲线下面积(AUC)评价IL-27对TPE的诊断准确性。此外,我们通过重新抽样纳入标准中不同年龄上限的患者,研究年龄对IL-27诊断效能的影响。结果:211名受试者中,TPE患者33名,非TPE患者178名。TPE患者IL-27的平均浓度明显高于非TPE患者。IL-27的AUC为0.76 (95% CI: 0.67 ~ 0.86)。在500 pg/mL阈值下,IL-27的敏感性和特异性分别为0.26 (95% CI: 0.20 ~ 0.33)和0.91 (95% CI:0.76 ~ 0.97)。年龄上限为70岁的患者IL-27的AUC为0.84。然而,在年龄上限为75岁的患者中,它降至0.76。结论:年龄会影响IL-27对TPE的诊断效能。
{"title":"Accuracy of interleukin-27 in diagnosing tuberculous pleural effusion: Age should be considered","authors":"Hong-Zhe Zhu ,&nbsp;Yan Niu ,&nbsp;Jian-Xun Wen ,&nbsp;Cheng Yan ,&nbsp;Su-Na Cha ,&nbsp;Yue Gao ,&nbsp;Xu-Lei Hao ,&nbsp;Wen-Jie Hou ,&nbsp;Li Yan ,&nbsp;Ting-Wang Jiang ,&nbsp;Zhi-De Hu ,&nbsp;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}
引用次数: 0
Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization 探索炎症细胞因子、代谢物和白塞综合征之间的因果关系:孟德尔随机化。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
白塞氏综合征是一种累及多系统的血管疾病,常诱发口腔黏膜溃疡。然而,炎性细胞因子和代谢物的水平与疾病发生的可能性是未知的。本研究旨在通过孟德尔随机化分析揭示细胞因子和代谢物与白塞综合征之间的因果关系。材料与方法:本研究采用工具变量单核苷酸多态性(snp),分别显示了91种细胞因子与553种代谢物之间的相关性。为探讨这些暴露因素与白歇综合征的因果关系,采用随机效应方差反加权法。此外,采用Cochran’s Q检验、异质性检验、水平多效性检验和MR-Egger截距检验进行敏感性分析,评价研究结果的稳健性和有效性。结果:共鉴定出5种物质与白塞综合征有因果关系,分别是细胞因子白介素12亚单位β (IL-12B)和白介素-33(IL-33),代谢物甘露醇,X-12728,双烯丙基与双键的比值。此外,没有明显的证据表明异质性或多效性。结论:我们的研究增加了目前关于特定炎症细胞因子和代谢物在白塞综合征病因学中的作用的知识。所鉴定的细胞因子和代谢物可作为临床筛选和预防白塞综合征的标志物,也可作为未来机制探索和药物靶点选择的候选分子。需要进一步的验证来评估这些细胞因子和代谢物作为预防白塞氏综合征的药理学靶点的潜力。
{"title":"Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization","authors":"Jiaqi Kong ,&nbsp;Xinpeng Liu ,&nbsp;Huishu Li ,&nbsp;Chubo Yang ,&nbsp;Tao Jiang ,&nbsp;Ying Yan ,&nbsp;Nan Miao ,&nbsp;Sen Mu ,&nbsp;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}
引用次数: 0
Seasonal shifts in respiratory pathogen co-infections and the associated differential induction of cytokines in children 呼吸道病原体合并感染的季节变化和儿童细胞因子的相关差异诱导。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
在大流行后时代,呼吸系统疾病的研究应重新关注严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)以外的病原体。呼吸道病原体,对儿童具有高度传染性,有不同的感染方式,如单一病原体感染和合并感染。了解这些病原体的季节性模式,以及确定单一感染和合并感染及其对儿童免疫状态的影响,对儿童的临床诊断、治疗和预后至关重要。我们的研究发现,从2023年12月到2024年4月,儿童的主要合并感染组合从肺炎支原体和流感病毒A (MP + IVA)转变为百日咳博德泰拉和鼻病毒(BP + RhV)。为了探讨这些感染的影响,我们建立了两个队列,分析MP、IVA、BP和RhV四种呼吸道病原体单独感染和共同感染对儿科患者免疫状态的影响。使用多细胞因子分析,细胞因子,如PDGF-BB,在单一感染和合并感染患者之间的差异表达被确定。此外,我们观察到单一病原体感染的儿童通常表现出更严重的病情,这可以通过比合并感染的儿童更高的总体细胞因子表达来证明。本研究结果为了解呼吸道病原菌单一感染和合并感染的致病机制,以及临床区分小儿各种呼吸道感染提供了重要的理论依据。
{"title":"Seasonal shifts in respiratory pathogen co-infections and the associated differential induction of cytokines in children","authors":"Yang Han ,&nbsp;Delong Wang ,&nbsp;Qian Wang ,&nbsp;Ying Liu ,&nbsp;Mingzhe Yan ,&nbsp;Fuli Ren ,&nbsp;Xujuan Hu ,&nbsp;Rui Gong ,&nbsp;Huadong Li ,&nbsp;Jingwen He ,&nbsp;Yaling Jia ,&nbsp;Jun Wan ,&nbsp;Gangyu Long ,&nbsp;Kaidi Nan ,&nbsp;Chaolin Huang ,&nbsp;Congrui Xu ,&nbsp;Qun Yao ,&nbsp;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}
引用次数: 0
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]
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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 ,&nbsp;Yu-chi Zhang ,&nbsp;Dao-feng Zheng ,&nbsp;Mu Zhang ,&nbsp;Hang Liu ,&nbsp;Miao He ,&nbsp;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}
引用次数: 0
Interferon therapy in alpha and Delta variants of SARS-CoV-2: The dichotomy between laboratory success and clinical realities 干扰素治疗SARS-CoV-2 α和δ变体:实验室成功与临床现实之间的二分法
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 10.1016/j.cyto.2024.156829
Atefe Alirezaee , Milad Mirmoghtadaei , Hanieh Heydarlou , Asiye Akbarian , Zahra Alizadeh
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.
COVID-19大流行在世界范围内造成了严重的发病率和死亡率。SARS-CoV-2的α和δ变体的出现重新引起了人们对使用干扰素治疗作为潜在治疗选择的兴趣。干扰素是宿主细胞对病毒感染产生的一组信号蛋白。它们通过在被感染细胞和邻近细胞中诱导抗病毒状态,在对病毒感染的先天免疫反应中发挥关键作用。干扰素治疗已显示出作为COVID-19潜在治疗选择的希望。在这篇综述文章中,我们回顾了目前在SARS-CoV-2 α和δ变体背景下有关干扰素治疗的知识,并讨论了将实验室发现转化为有效临床治疗必须克服的挑战。
{"title":"Interferon therapy in alpha and Delta variants of SARS-CoV-2: The dichotomy between laboratory success and clinical realities","authors":"Atefe Alirezaee ,&nbsp;Milad Mirmoghtadaei ,&nbsp;Hanieh Heydarlou ,&nbsp;Asiye Akbarian ,&nbsp;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}
引用次数: 0
Circulating inflammatory markers predict depressive symptomatology in COVID-19 survivors 循环炎症标志物预测COVID-19幸存者的抑郁症状
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
越来越多的证据表明,支持covid -19后抑郁的神经生物学机制主要与免疫反应和随后未解决的低度炎症有关。在此,我们利用在感染后1个月和3个月在COVID-19幸存者中测量的广泛的细胞因子血清水平来预测COVID-19后抑郁。在圣拉斐尔医院,通过贝克抑郁量表(BDI-13)和Zung抑郁自评量表(ZSDS),对87名COVID - 19幸存者在出院后1个月和3个月进行抑郁症状筛查。在两个时间点采集血液样本并通过Luminex进行分析。我们将为期一个月的42种炎症化合物输入到两个单独的惩罚逻辑回归模型中,以评估它们在识别两个时间点患有临床抑郁症的COVID-19幸存者方面的可靠性,并在机器学习常规中应用。分析物在时间点之间降低的δ值被输入到第三个预测存在长期抑郁的模型中。计算5000个bootstrap来确定预测因子的显著性。横截面模型的平衡精度(BA)达到76%,灵敏度达到70%。高水平的CCL17、CCL22可预测covid -19后抑郁。另一方面,CXCL10、CCL2、CCL3、CCL8、CXCL5、CCL15、CCL23、CXCL13和GM-CSF均表现出保护作用。纵向模型也获得了良好的表现(BA = 74%, sensitivity = 68%),揭示了CXCL16和CCL25是临床抑郁的额外驱动因素。此外,分析物随时间的动态变化准确预测长期抑郁(BA = 76%,灵敏度= 75%)。我们的研究结果揭示了一种假定的支持covid -19后抑郁症的免疫特征,从而加强了深化分子机制以适当靶向抑郁症的必要性。
{"title":"Circulating inflammatory markers predict depressive symptomatology in COVID-19 survivors","authors":"Mariagrazia Palladini ,&nbsp;Mario Gennaro Mazza ,&nbsp;Rebecca De Lorenzo ,&nbsp;Sara Spadini ,&nbsp;Veronica Aggio ,&nbsp;Margherita Bessi ,&nbsp;Federico Calesella ,&nbsp;Beatrice Bravi ,&nbsp;Patrizia Rovere-Querini ,&nbsp;Francesco Benedetti ,&nbsp;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}
引用次数: 0
Exploring the causal relationship between inflammatory cytokines and myasthenia gravis: A two-way Mendelian randomization study 探讨炎症细胞因子与重症肌无力之间的因果关系:一项双向孟德尔随机研究。
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 DOI: 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.
背景:根据以往的研究,重症肌无力(MG)与慢性炎症有关。然而,炎症因子与MG发生之间关系的确切性质尚不清楚。因此,本研究的目的是探讨受遗传因素影响的炎症因子水平的改变是否与MG的发生有关。这将通过双样本孟德尔随机化(MR)分析来实现。方法:我们进行了一项双向孟德尔随机化(MR)研究,利用全基因组关联研究(GWAS)的遗传数据,包括1873例MG病例和36,370名欧洲血统的个体作为对照。炎症因子的数据来自8293名健康参与者的GWAS数据。反方差加权(IVW)方法主要用于调查暴露与结果之间的因果关系。此外,采用MR-Egger、加权中位数、简单模型、加权模型、MR-PRESSO等多种敏感性分析方法来加强结果的可靠性。通过这些严格的方法,我们广泛地研究了炎症因子和MG之间的关系;然而,需要进一步的研究来确定具体的因果关系。结果:应用Bonferroni校正后,遗传预测显示γ干扰素(MIG)诱导的单因子与MG之间存在显著相关性(OR: 1.09, 95% CI: 1.04-1.14;p = 0.0006)。此外,初步发现Eotaxin和白细胞介素-2受体拮抗剂(IL-2ra)与MG存在正相关遗传关系(OR: 0.81, 95% CI: 0.66-0.99, P = 0.044;Or: 0.80, 95% ci: 0.68-0.94, p = 0.008)。反向MR分析提供了MIP1α、GROa、IL-13、TRAIL、IL-2ra和IL-1ra与MG发展之间关联的初步证据。遗传变异之间没有多效性或异质性的迹象(P < 0.05)。结论:本研究揭示了炎症细胞因子与MG之间的新联系,揭示了导致该疾病发展的潜在因素。Eotaxin和IL-2ra水平升高与MG的高风险相关,同时表明MIG、MIP1α、GROa、IL-13、TRAIL、IL-2ra和IL-1ra可能因MG而升高,尤其是MIG。这些发现表明,靶向和调节特定的炎症因子可能为治疗和预防MG提供有希望的途径。
{"title":"Exploring the causal relationship between inflammatory cytokines and myasthenia gravis: A two-way Mendelian randomization study","authors":"Jing-Yu Li ,&nbsp;Yan-Jun Ling ,&nbsp;Wen-Hui Bao ,&nbsp;Wen-Na Zhang ,&nbsp;Xin-Miao Han ,&nbsp;Xiao-Chen Zheng ,&nbsp;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> &gt; 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}
引用次数: 0
期刊
Cytokine
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1