CSF IL-6 in children with neuroinflammatory conditions

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.

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.

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.

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.