BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspect...BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.展开更多
目的通过证据图描述和总结白介素-6(IL-6)/白介素-6受体(IL-6R)与多种健康结局孟德尔随机化研究中的证据,明确其分布,以期为该领域研究提供参考。方法系统检索PubMed、EMBASE、Web of Science、Scopus、中国知识基础设施工程、中国生物...目的通过证据图描述和总结白介素-6(IL-6)/白介素-6受体(IL-6R)与多种健康结局孟德尔随机化研究中的证据,明确其分布,以期为该领域研究提供参考。方法系统检索PubMed、EMBASE、Web of Science、Scopus、中国知识基础设施工程、中国生物医学文献服务系统、万方数据库、维普数据库中IL-6/IL-6R与多种疾病的孟德尔随机化研究,采用图表结合形式综合分析和展示纳入研究的基本信息、研究方法和研究结局。结果最终纳入38篇孟德尔随机化研究,2020年以后相关研究数增加趋势明显,纳入研究探讨IL-6、IL-6R、sIL-6R、gp130、IL-6RA 5种不同的表型和65种不同疾病间的因果关系。其中,遗传预测的IL-6水平与终末期肾病、精神分裂症、冠状动脉疾病和心房颤动存在因果关系,IL-6R与黑色素瘤、髓系白血病、膀胱癌、喉癌、眼癌和胆囊癌的发生率存在因果关系,sIL-6R水平与肺动脉高压、哮喘、抑郁、多发性硬化症、腹主动脉瘤等疾病患病率存在因果关系。结论孟德尔随机化研究提供了关于IL-6/IL-6R在多种健康结局中的因果作用的重要证据,涵盖精神心理、炎症、癌症和心血管疾病等,反映了IL-6/IL-6R在多种疾病中的广泛影响和IL-6领域研究的重要性。展开更多
文摘BACKGROUND The interplay between inflammation,immune dysregulation,and the onset of neurological disorders,including epilepsy,has become increasingly recognized.Interleukin(IL)-6,a pro-inflammatory cytokine,is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients.The role of IL-6 receptor(IL6R)blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.neuropsychiatric conditions due to neuroinflammation.METHODS Mendelian randomization(MR)analysis employing single nucleotide poly-morphisms(SNPs)in the vicinity of the IL6R gene(total individuals=408225)was used to evaluate the putative causal relationship between IL6R blockade and epilepsy(total cases/controls=12891/312803),focal epilepsy(cases/controls=7526/399290),and generalized epilepsy(cases/controls=1413/399287).SNP weights were determined by their effect on C-reactive protein(CRP)levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects.To address potential outlier and pleiotropic influences,sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.RESULTS The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk[inverse variance weighting:Odds ratio(OR):0.827;95%confidence interval(CI):0.685-1.000;P=0.05].Subtype analysis showed variability,with no significant effect observed in generalized,focal,or specific childhood and juvenile epilepsy forms.Beyond the primary inflammatory marker CRP,the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy,hinting at possible links to neuroinflammation,psychiatric symptoms,and associated mental disorders.CONCLUSION The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence,likely mediated via complex neuroinflammatory pathways.These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy.The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.
文摘目的通过证据图描述和总结白介素-6(IL-6)/白介素-6受体(IL-6R)与多种健康结局孟德尔随机化研究中的证据,明确其分布,以期为该领域研究提供参考。方法系统检索PubMed、EMBASE、Web of Science、Scopus、中国知识基础设施工程、中国生物医学文献服务系统、万方数据库、维普数据库中IL-6/IL-6R与多种疾病的孟德尔随机化研究,采用图表结合形式综合分析和展示纳入研究的基本信息、研究方法和研究结局。结果最终纳入38篇孟德尔随机化研究,2020年以后相关研究数增加趋势明显,纳入研究探讨IL-6、IL-6R、sIL-6R、gp130、IL-6RA 5种不同的表型和65种不同疾病间的因果关系。其中,遗传预测的IL-6水平与终末期肾病、精神分裂症、冠状动脉疾病和心房颤动存在因果关系,IL-6R与黑色素瘤、髓系白血病、膀胱癌、喉癌、眼癌和胆囊癌的发生率存在因果关系,sIL-6R水平与肺动脉高压、哮喘、抑郁、多发性硬化症、腹主动脉瘤等疾病患病率存在因果关系。结论孟德尔随机化研究提供了关于IL-6/IL-6R在多种健康结局中的因果作用的重要证据,涵盖精神心理、炎症、癌症和心血管疾病等,反映了IL-6/IL-6R在多种疾病中的广泛影响和IL-6领域研究的重要性。
