{"title":"CSF IL-6 in children with neuroinflammatory conditions","authors":"Valeria Pozzilli , Manori Prasadani Thambiliyagodage , Kshitij Mankad , Austen Worth , Paul Brogan , Sara Ghorashian , Alasdair Bamford , Cheryl Hemingway , Marios Kaliakatsos , Kimberly Gilmour , Yael Hacohen","doi":"10.1016/j.ejpn.2025.07.013","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>Cerebrospinal fluid <strong>(</strong>CSF) cytokines may contribute to immune-mediated processes affecting the central nervous system (CNS). We evaluated CSF cytokine profiles in children with suspected neuroinflammatory conditions to explore their clinical relevance.</div></div><div><h3>Methods</h3><div>Between 2019 and 2024, CSF from children <18 years were analyzed using BD Biosciences cytokine bead array for interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-alpha (IFN-α), and tumour necrosis-factor-alpha (TNF-α). Clinical phenotyping was conducted. Serum cytokine levels were measured in cases with abnormal CSF, when available.</div></div><div><h3>Results</h3><div>112 patients were included (median age 6 years [IQR 3.6–11.2]; 54 % male). CSF IL-6 was raised in 35/112 (31 %; median 107 pg/ml, IQR 24–329). No other cytokine was raised without concurrent IL-6. Raised CSF IL-6 occurred in 16/50 acquired neuroimmune conditions (including myelin oligodendrocyte glycoprotein antibody-associated disease, seronegative demyelination, seronegative autoimmune encephalitis, and febrile-infection-related epilepsy syndrome), 5/9 CNS infections; 9/17 monogenic autoinflammatory syndromes, and 5/7 cancer treatment-related neurotoxicities.</div><div>Of the 35 patients with raised CSF IL-6, 21 had serum cytokines tested; 13 (62 %) showed elevated serum IL-6. In demyelinating cases, higher IL-6 was associated with increased CSF protein (p = 0.007). Follow-up CSF samples (n = 16, median 34 days) showed persistent elevation in 7 and normalisation in 9. IL-6 inhibitors (tocilizumab and/or siltuximab) were used in 10 patients with variable outcomes, depending on the underlying etiology.</div></div><div><h3>Conclusions</h3><div>CSF IL-6 was the most frequently elevated cytokine in our cohort, observed across a range of primary and secondary neuroinflammatory disorders. While not diagnostic of a specific condition, its elevation may help guide treatment decisions.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"58 ","pages":"Pages 42-49"},"PeriodicalIF":2.3000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Paediatric Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1090379825001254","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction
Cerebrospinal fluid (CSF) cytokines may contribute to immune-mediated processes affecting the central nervous system (CNS). We evaluated CSF cytokine profiles in children with suspected neuroinflammatory conditions to explore their clinical relevance.
Methods
Between 2019 and 2024, CSF from children <18 years were analyzed using BD Biosciences cytokine bead array for interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-alpha (IFN-α), and tumour necrosis-factor-alpha (TNF-α). Clinical phenotyping was conducted. Serum cytokine levels were measured in cases with abnormal CSF, when available.
Results
112 patients were included (median age 6 years [IQR 3.6–11.2]; 54 % male). CSF IL-6 was raised in 35/112 (31 %; median 107 pg/ml, IQR 24–329). No other cytokine was raised without concurrent IL-6. Raised CSF IL-6 occurred in 16/50 acquired neuroimmune conditions (including myelin oligodendrocyte glycoprotein antibody-associated disease, seronegative demyelination, seronegative autoimmune encephalitis, and febrile-infection-related epilepsy syndrome), 5/9 CNS infections; 9/17 monogenic autoinflammatory syndromes, and 5/7 cancer treatment-related neurotoxicities.
Of the 35 patients with raised CSF IL-6, 21 had serum cytokines tested; 13 (62 %) showed elevated serum IL-6. In demyelinating cases, higher IL-6 was associated with increased CSF protein (p = 0.007). Follow-up CSF samples (n = 16, median 34 days) showed persistent elevation in 7 and normalisation in 9. IL-6 inhibitors (tocilizumab and/or siltuximab) were used in 10 patients with variable outcomes, depending on the underlying etiology.
Conclusions
CSF IL-6 was the most frequently elevated cytokine in our cohort, observed across a range of primary and secondary neuroinflammatory disorders. While not diagnostic of a specific condition, its elevation may help guide treatment decisions.
期刊介绍:
The European Journal of Paediatric Neurology is the Official Journal of the European Paediatric Neurology Society, successor to the long-established European Federation of Child Neurology Societies.
Under the guidance of a prestigious International editorial board, this multi-disciplinary journal publishes exciting clinical and experimental research in this rapidly expanding field. High quality papers written by leading experts encompass all the major diseases including epilepsy, movement disorders, neuromuscular disorders, neurodegenerative disorders and intellectual disability.
Other exciting highlights include articles on brain imaging and neonatal neurology, and the publication of regularly updated tables relating to the main groups of disorders.