{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:33:52Z","timestamp":1790980432605,"version":"4.1.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T00:00:00Z","timestamp":1752537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100002352","name":"Ain Shams University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002352","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Multiple Sclerosis (MS) is a chronic immune-mediated neurological disorder frequently accompanied by cognitive impairment, which affects up to 60% of patients and is associated with faster disease progression and greater disability. Interleukin-6 (IL-6), a key proinflammatory cytokine involved in neuroinflammation, has been implicated in MS pathogenesis, and the rs1800795 (\u2212174 G&gt;C) single nucleotide polymorphism (SNP) in the IL6 gene may influence disease susceptibility and clinical severity. This study investigated the association between the IL6 rs1800795 polymorphism and clinical outcomes in Epstein-Barr virus (EBV)-positive MS patients, with a particular focus on cognitive dysfunction. A case-control design was employed, including 300 participants: 150 EBV-positive MS patients and 150 matched healthy controls. Genotyping was performed using TaqMan-based PCR, and clinical data such as disability status, disease progression, and cognitive performance were analyzed. The CC genotype was significantly more frequent in MS patients and was associated with a higher risk of severe disability (OR = 6.11, <jats:italic>p<\/jats:italic> = 0.0004), faster disease progression, and increased likelihood of cognitive impairment. These findings suggest that the IL6 rs1800795 polymorphism, particularly the CC genotype, contributes to MS susceptibility and adverse clinical outcomes. IL6 genotyping may hold promise as a predictive tool for disease progression and cognitive decline in EBV-associated MS, offering insights for more personalized therapeutic strategies.<\/jats:p>","DOI":"10.1007\/s12035-025-05211-x","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T03:39:04Z","timestamp":1752550744000},"page":"14089-14100","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the Link Between IL-6 rs1800795 G &gt; C SNP and the Severity of Epstein-Barr Virus-Associated Multiple Sclerosis: Potential Impact on Cognitive Impairment"],"prefix":"10.1007","volume":"62","author":[{"given":"Tokka M.","family":"Hassan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azza M.","family":"El Amir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahla Elsayed","family":"Nagy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6646-4674","authenticated-orcid":false,"given":"Nashwa","family":"El-Khazragy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,15]]},"reference":[{"key":"5211_CR1","doi-asserted-by":"publisher","first-page":"100039","DOI":"10.1016\/j.jtauto.2020.100039","volume":"3","author":"S Cavallo","year":"2020","unstructured":"Cavallo S (2020) Immune-mediated genesis of multiple sclerosis. J Transl Autoimmun 3:100039. https:\/\/doi.org\/10.1016\/j.jtauto.2020.100039","journal-title":"J Transl Autoimmun"},{"issue":"14","key":"5211_CR2","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1177\/1352458520970841","volume":"26","author":"C Walton","year":"2020","unstructured":"Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA et al (2020) Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler 26(14):1816\u20131821. https:\/\/doi.org\/10.1177\/1352458520970841","journal-title":"Mult Scler"},{"key":"5211_CR3","doi-asserted-by":"publisher","first-page":"106207","DOI":"10.1016\/j.msard.2024.106207","volume":"93","author":"CMC Lemmens","year":"2025","unstructured":"Lemmens CMC, Vanhommerig JW, Knottnerus BJ, Uitdehaag BMJ, Mostert JP, de Jong BA (2025) Prevalence and incidence of multiple sclerosis in the Netherlands. Mult Scler Relat Disord 93:106207. https:\/\/doi.org\/10.1016\/j.msard.2024.106207","journal-title":"Mult Scler Relat Disord"},{"issue":"1","key":"5211_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/cei\/uxad075","volume":"214","author":"JM van Noort","year":"2023","unstructured":"van Noort JM, Baker D, Kipp M, Amor S (2023) The pathogenesis of multiple sclerosis: a series of unfortunate events. Clin Exp Immunol 214(1):1\u201317. https:\/\/doi.org\/10.1093\/cei\/uxad075","journal-title":"Clin Exp Immunol"},{"issue":"11","key":"5211_CR5","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.3390\/jcm13113321","volume":"13","author":"S G\u00f3mez-Melero","year":"2024","unstructured":"G\u00f3mez-Melero S, Caballero-Villarraso J, Escribano BM, Galvao-Carmona A, T\u00fanez I, Ag\u00fcera-Morales E (2024) Impact of Cognitive Impairment on Quality of Life in Multiple Sclerosis Patients\u2014A Comprehensive Review. J Clin Med 13(11):3321. https:\/\/doi.org\/10.3390\/jcm13113321","journal-title":"J Clin Med"},{"issue":"6","key":"5211_CR6","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1055\/s-0043-1763485","volume":"81","author":"C Piacentini","year":"2023","unstructured":"Piacentini C, Argento O, Nocentini U (2023) Cognitive impairment in multiple sclerosis: \u201cclassic\u201d knowledge and recent acquisitions. Arq Neuropsiquiatr 81(6):585\u2013596. https:\/\/doi.org\/10.1055\/s-0043-1763485","journal-title":"Arq Neuropsiquiatr"},{"issue":"6","key":"5211_CR7","doi-asserted-by":"publisher","first-page":"e1454","DOI":"10.1002\/cti2.1454","volume":"12","author":"A Afrasiabi","year":"2023","unstructured":"Afrasiabi A, Ahlenstiel C, Swaminathan S, Parnell GP (2023) The interaction between Epstein\u2013Barr virus and multiple sclerosis gene tic risk loci: insights into disease pathogenesis and therapeutic opportunities. Clin Transl Immunol 12(6):e1454. https:\/\/doi.org\/10.1002\/cti2.1454","journal-title":"Clin Transl Immunol"},{"issue":"9","key":"5211_CR8","doi-asserted-by":"publisher","first-page":"101497","DOI":"10.1016\/j.disamonth.2022.101497","volume":"69","author":"A Shah","year":"2023","unstructured":"Shah A, Panchal V, Patel K, Alimohamed Z, Kaka N, Sethi Y et al (2023) Pathogenesis and management of multiple sclerosis revisited. Disease-a-Month 69(9):101497. https:\/\/doi.org\/10.1016\/j.disamonth.2022.101497","journal-title":"Disease-a-Month"},{"issue":"8","key":"5211_CR9","doi-asserted-by":"publisher","first-page":"2399","DOI":"10.1002\/hbm.25375","volume":"42","author":"C Tsagkas","year":"2021","unstructured":"Tsagkas C, Parmar K, Pezold S, Barro C, Chakravarty MM, Gaetano L et al (2021) Classification of multiple sclerosis based on patterns of CNS regional atrophy covariance. Hum Brain Mapp 42(8):2399\u20132415. https:\/\/doi.org\/10.1002\/hbm.25375","journal-title":"Hum Brain Mapp"},{"key":"5211_CR10","doi-asserted-by":"publisher","first-page":"100977","DOI":"10.1016\/j.lanepe.2024.100977","volume":"44","author":"E Portaccio","year":"2024","unstructured":"Portaccio E, Magyari M, Havrdova EK, Ruet A, Brochet B, Scalfari A et al (2024) Multiple sclerosis: emerging epidemiological trends and redefining the clinical course. Lancet Reg Health - Europe 44:100977. https:\/\/doi.org\/10.1016\/j.lanepe.2024.100977","journal-title":"Lancet Reg Health - Europe"},{"key":"5211_CR11","doi-asserted-by":"publisher","first-page":"594","DOI":"10.3389\/fnins.2019.00594","volume":"13","author":"A Marzullo","year":"2019","unstructured":"Marzullo A, Kocevar G, Stamile C, Durand-Dubief F, Terracina G, Calimeri F et al (2019) Classification of Multiple Sclerosis Clinical Profiles via Graph Convo lutional Neural Networks. Front Neurosci 13:594. https:\/\/doi.org\/10.3389\/fnins.2019.00594","journal-title":"Front Neurosci"},{"issue":"4","key":"5211_CR12","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1016\/s1474-4422(22)00471-9","volume":"22","author":"F Aloisi","year":"2023","unstructured":"Aloisi F, Giovannoni G, Salvetti M (2023) Epstein-Barr virus as a cause of multiple sclerosis: opportunities for prevention and therapy. Lancet Neurol 22(4):338\u2013349. https:\/\/doi.org\/10.1016\/s1474-4422(22)00471-9","journal-title":"Lancet Neurol"},{"key":"5211_CR13","doi-asserted-by":"publisher","first-page":"1212676","DOI":"10.3389\/fimmu.2023.1212676","volume":"14","author":"AK Hedstr\u00f6m","year":"2023","unstructured":"Hedstr\u00f6m AK (2023) Risk factors for multiple sclerosis in the context of Epstein-Barr virus infection. Front Immunol 14:1212676. https:\/\/doi.org\/10.3389\/fimmu.2023.1212676","journal-title":"Front Immunol"},{"issue":"12","key":"5211_CR14","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.tig.2017.09.004","volume":"33","author":"SE Baranzini","year":"2017","unstructured":"Baranzini SE, Oksenberg JR (2017) The Genetics of Multiple Sclerosis: From 0 to 200 in 50 Years. Trends Genet 33(12):960\u2013970. https:\/\/doi.org\/10.1016\/j.tig.2017.09.004","journal-title":"Trends Genet"},{"issue":"23","key":"5211_CR15","doi-asserted-by":"publisher","first-page":"12906","DOI":"10.3390\/ijms252312906","volume":"25","author":"B Arneth","year":"2024","unstructured":"Arneth B (2024) Genes, Gene Loci, and Their Impacts on the Immune System in the Development of Multiple Sclerosis: A Systematic Review. Int J Mol Sci 25(23):12906. https:\/\/doi.org\/10.3390\/ijms252312906","journal-title":"Int J Mol Sci"},{"issue":"3","key":"5211_CR16","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s13760-018-0994-9","volume":"118","author":"Y Bene\u0161ov\u00e1","year":"2018","unstructured":"Bene\u0161ov\u00e1 Y, Va\u0161k\u016f A, Bienertov\u00e1-Va\u0161k\u016f J (2018) Association of interleukin 6, interleukin 7 receptor alpha, and interl eukin 12B gene polymorphisms with multiple sclerosis. Acta Neurol Belg 118(3):493\u2013501. https:\/\/doi.org\/10.1007\/s13760-018-0994-9","journal-title":"Acta Neurol Belg"},{"issue":"5","key":"5211_CR17","doi-asserted-by":"publisher","first-page":"897","DOI":"10.3390\/genes13050897","volume":"13","author":"A Bruno","year":"2022","unstructured":"Bruno A, Dolcetti E, Azzolini F, Moscatelli A, Gambardella S, Ferese R et al (2022) Interleukin 6 SNP rs1818879 Regulates Radiological and Inflammatory Activity in Multiple Sclerosis. Genes 13(5):897. https:\/\/doi.org\/10.3390\/genes13050897","journal-title":"Genes"},{"key":"5211_CR18","doi-asserted-by":"publisher","first-page":"407","DOI":"10.4236\/ojgen.2014.45038","volume":"4","author":"M Pourhossein","year":"2014","unstructured":"Pourhossein M, Ghavimi R, Alsahebfosoul F, Ghaedi K (2014) Association between rs1800795 (-174 G\/C) Polymorphism in the Promoter of IL6 Gene and Risk of Relapsing-Remitting Multiple Sclerosis (RRMS) in Isfahan Population. Open J Genet 4:407\u2013413. https:\/\/doi.org\/10.4236\/ojgen.2014.45038","journal-title":"Open J Genet"},{"issue":"2","key":"5211_CR19","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1089\/gtmb.2013.0387","volume":"18","author":"S Hu","year":"2014","unstructured":"Hu S, Chen Y, Sun X-D, Li F-J, Shu Q-F, Liu X-L et al (2014) Association Between IL-6-174G\/C Polymorphism and Risk of Multip le Sclerosis: A Meta-Analysis. Genet Test Mol Biomarkers 18(2):127\u2013130. https:\/\/doi.org\/10.1089\/gtmb.2013.0387","journal-title":"Genet Test Mol Biomarkers"},{"key":"5211_CR20","doi-asserted-by":"publisher","first-page":"103008","DOI":"10.1016\/j.msard.2021.103008","volume":"52","author":"D Varvatsi","year":"2021","unstructured":"Varvatsi D, Richter J, Tryfonos C, Pantzaris M, Christodoulou C (2021) Association of Epstein-Barr virus latently expressed genes with multiple sclerosis. Mult Scler Relat Disord 52:103008. https:\/\/doi.org\/10.1016\/j.msard.2021.103008","journal-title":"Mult Scler Relat Disord"},{"key":"5211_CR21","doi-asserted-by":"publisher","first-page":"834644","DOI":"10.3389\/fimmu.2022.834644","volume":"13","author":"M Vandebergh","year":"2022","unstructured":"Vandebergh M, Becelaere S, Group CIW, Dubois B, Goris A (2022) Body Mass Index, Interleukin-6 Signaling and Multiple Sclerosis: A Men delian Randomization Study. Front Immunol 13:834644. https:\/\/doi.org\/10.3389\/fimmu.2022.834644","journal-title":"Front Immunol"},{"issue":"3","key":"5211_CR22","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1159\/000522577","volume":"65","author":"R Kianfar","year":"2022","unstructured":"Kianfar R, Ravanshad M, Ghiass MA, Rafiee N, Shayeghpour A, Maleki A (2022) Evaluation of IL-1\u03b2 and IL-6 Expression following EBNA-1 and BRLF-1 Pe ptide Treatment in Epstein-Barr Virus-Positive Multiple Sclerosis Patients. Intervirology 65(3):144\u2013150. https:\/\/doi.org\/10.1159\/000522577","journal-title":"Intervirology"},{"issue":"10","key":"5211_CR23","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1016\/S1474-4422(20)30277-5","volume":"19","author":"RHB Benedict","year":"2020","unstructured":"Benedict RHB, Amato MP, DeLuca J, Geurts JJG (2020) Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues. Lancet Neurol 19(10):860\u2013871. https:\/\/doi.org\/10.1016\/S1474-4422(20)30277-5","journal-title":"Lancet Neurol"},{"key":"5211_CR24","doi-asserted-by":"publisher","first-page":"102701","DOI":"10.1016\/j.msard.2020.102701","volume":"48","author":"LCP Gois","year":"2021","unstructured":"Gois LCP, Pimentel-Silva LR, Damasceno BP, Damasceno A (2021) Associations between cognitive and clinical disability across MS subtypes: The role of the underlying brain damage. Mult Scler Relat Disord 48:102701. https:\/\/doi.org\/10.1016\/j.msard.2020.102701","journal-title":"Mult Scler Relat Disord"},{"issue":"1","key":"5211_CR25","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/biom15010068","volume":"15","author":"B Gajewski","year":"2025","unstructured":"Gajewski B, Karli\u0144ska I, Domowicz M, Bednarski I, \u015awiderek-Matysiak M, Stasio\u0142ek M (2025) No Relation Between Cognitive Impairment, Physical Disability and Seru m Biomarkers in a Cohort of Progressive Multiple Sclerosis Patients. Biomolecules 15(1):68. https:\/\/doi.org\/10.3390\/biom15010068","journal-title":"Biomolecules"},{"issue":"104","key":"5211_CR26","doi-asserted-by":"publisher","first-page":"eadl3604","DOI":"10.1126\/sciimmunol.adl3604","volume":"10","author":"J Sarkkinen","year":"2025","unstructured":"Sarkkinen J, Yohannes DA, Kreivi N, D\u00fcrnsteiner P, Elsakova A, Huuhtanen J et al (2025) Altered immune landscape of cervical lymph nodes reveals Epstein-Barr virus signature in multiple sclerosis. Sci Immunol 10(104):eadl3604. https:\/\/doi.org\/10.1126\/sciimmunol.adl3604","journal-title":"Sci Immunol"},{"issue":"1","key":"5211_CR27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s00284-022-03112-z","volume":"80","author":"S Sedighi","year":"2022","unstructured":"Sedighi S, Gholizadeh O, Yasamineh S, Akbarzadeh S, Amini P, Favakehi P et al (2022) Comprehensive Investigations Relationship Between Viral Infections and Multiple Sclerosis Pathogenesis. Curr Microbiol 80(1):15. https:\/\/doi.org\/10.1007\/s00284-022-03112-z","journal-title":"Curr Microbiol"},{"issue":"4","key":"5211_CR28","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1007\/s11064-023-04085-6","volume":"49","author":"C Shan","year":"2024","unstructured":"Shan C, Zhang C, Zhang C (2024) The Role of IL-6 in Neurodegenerative Disorders. Neurochem Res 49(4):834\u2013846. https:\/\/doi.org\/10.1007\/s11064-023-04085-6","journal-title":"Neurochem Res"},{"key":"5211_CR29","doi-asserted-by":"publisher","first-page":"155582","DOI":"10.1016\/j.cyto.2021.155582","volume":"144","author":"KK Kummer","year":"2021","unstructured":"Kummer KK, Zeidler M, Kalpachidou T, Kress M (2021) Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine. 144:155582. https:\/\/doi.org\/10.1016\/j.cyto.2021.155582","journal-title":"Cytokine."},{"issue":"1-2","key":"5211_CR30","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.jneuroim.2010.08.003","volume":"230","author":"C Casiraghi","year":"2011","unstructured":"Casiraghi C, Dorovini-Zis K, Horwitz MS (2011) Epstein-Barr virus infection of human brain microvessel endothelial cells: A novel role in multiple sclerosis. J Neuroimmunol 230(1-2):173\u2013177. https:\/\/doi.org\/10.1016\/j.jneuroim.2010.08.003","journal-title":"J Neuroimmunol"},{"issue":"Suppl 1","key":"5211_CR31","doi-asserted-by":"publisher","first-page":"S69","DOI":"10.29399\/npa.23343","volume":"55","author":"BP \u00c7inar","year":"2018","unstructured":"\u00c7inar BP, Yorgun YG (2018) What We Learned from The History of Multiple Sclerosis Measurement: Expanded Disability Status Scale. Noro Psikiyatr Ars 55(Suppl 1):S69\u2013S75. https:\/\/doi.org\/10.29399\/npa.23343","journal-title":"Noro Psikiyatr Ars"},{"issue":"1","key":"5211_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s41983-023-00779-4","volume":"60","author":"MA Shawky","year":"2024","unstructured":"Shawky MA, Menecie TI, Saif El Deen EM, Rashad MH (2024) Predictors of progression of multiple sclerosis in a sample of Egyptian patients. Egypt J Neurol Psychiatry Neurosurg 60(1):1. https:\/\/doi.org\/10.1186\/s41983-023-00779-4","journal-title":"Egypt J Neurol Psychiatry Neurosurg"},{"issue":"2","key":"5211_CR33","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.rehab.2018.01.006","volume":"63","author":"A Ruet","year":"2020","unstructured":"Ruet A, Brochet B (2020) Cognitive assessment in patients with multiple sclerosis: From neuropsychological batteries to ecological tools. Ann Phys Rehabil Med 63(2):154\u2013158. https:\/\/doi.org\/10.1016\/j.rehab.2018.01.006","journal-title":"Ann Phys Rehabil Med"},{"issue":"4","key":"5211_CR34","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3390\/neurosci3040048","volume":"3","author":"E Portaccio","year":"2022","unstructured":"Portaccio E, Amato MP (2022) Cognitive Impairment in Multiple Sclerosis: An Update on Assessment and Management. NeuroSci 3(4):667\u2013676. https:\/\/doi.org\/10.3390\/neurosci3040048","journal-title":"NeuroSci"},{"key":"5211_CR35","doi-asserted-by":"publisher","first-page":"1557483","DOI":"10.3389\/fimmu.2025.1557483","volume":"16","author":"C Ballerini","year":"2025","unstructured":"Ballerini C, Amoriello R, Maghrebi O, Bellucci G, Addazio I, Betti M et al (2025) Exploring the role of EBV in multiple sclerosis pathogenesis through E. Front Immunol 16:1557483. https:\/\/doi.org\/10.3389\/fimmu.2025.1557483","journal-title":"Front Immunol"},{"key":"5211_CR36","doi-asserted-by":"publisher","first-page":"612953","DOI":"10.3389\/fncel.2020.612953","volume":"14","author":"L Ferr\u00e8","year":"2020","unstructured":"Ferr\u00e8 L, Filippi M, Esposito F (2020) Involvement of Genetic Factors in Multiple Sclerosis. Front Cell Neurosci 14:612953. https:\/\/doi.org\/10.3389\/fncel.2020.612953","journal-title":"Front Cell Neurosci"},{"key":"5211_CR37","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1016\/j.bbi.2015.08.016","volume":"51","author":"V Napolioni","year":"2016","unstructured":"Napolioni V, MacMurray J (2016) Infectious diseases, IL6 \u2212174G>C polymorphism, and human development. Brain Behav Immun 51:196\u2013203. https:\/\/doi.org\/10.1016\/j.bbi.2015.08.016","journal-title":"Brain Behav Immun"},{"key":"5211_CR38","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1016\/j.exger.2004.07.006","volume":"39","author":"C Capurso","year":"2004","unstructured":"Capurso C, Solfrizzi V, D\u2019Introno A, Colacicco A, Capurso S, Capurso A et al (2004) Interleukin 6-174 G\/C promoter gene polymorphism and sporadic Alzheimer's disease: Geographic allele and genotype variations in Europe. Exp Gerontol 39:1567\u20131573. https:\/\/doi.org\/10.1016\/j.exger.2004.07.006","journal-title":"Exp Gerontol"},{"issue":"1","key":"5211_CR39","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.jneuroim.2005.06.020","volume":"168","author":"S Mihailova","year":"2005","unstructured":"Mihailova S, Ivanova M, Mihaylova A, Quin L, Mikova O, Naumova E (2005) Pro- and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients. J Neuroimmunol 168(1):138\u2013143. https:\/\/doi.org\/10.1016\/j.jneuroim.2005.06.020","journal-title":"J Neuroimmunol"},{"issue":"1","key":"5211_CR40","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s12883-025-04145-0","volume":"25","author":"J Itorralba","year":"2025","unstructured":"Itorralba J, Brand-Arzamendi K, Saab G, Muccilli A, Schneider R (2025) Intrathecal interleukin-6 levels are associated with progressive disease and clinical severity in multiple sclerosis. BMC Neurol 25(1):136. https:\/\/doi.org\/10.1186\/s12883-025-04145-0","journal-title":"BMC Neurol"},{"key":"5211_CR41","doi-asserted-by":"publisher","unstructured":"Gruol D (2014) IL-6 Regulation of Synaptic Function in the CNS. Neuropharmacology:96. https:\/\/doi.org\/10.1016\/j.neuropharm.2014.10.023","DOI":"10.1016\/j.neuropharm.2014.10.023"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05211-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-025-05211-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-025-05211-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T07:34:08Z","timestamp":1759995248000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-025-05211-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,15]]},"references-count":41,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["5211"],"URL":"https:\/\/doi.org\/10.1007\/s12035-025-05211-x","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,15]]},"assertion":[{"value":"2 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Research Ethics Committee at the Faculty of Medicine, Ain Shams University, approval No: FMASU MS263\/2024. Informed consent was obtained from all participants prior to their involvement in the study. The study was performed following all relevant ethical standards of the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent for Participate"}},{"value":"Consent has been given by all authors for publication of this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}