IL-1β contributes to neurological disability in NMOSD AQP4 + Patients

Background: Neuromyelitis Optica Spectrum Disorder (NMOSD) is a central nervous system inflammatory disease that causes severe disability. Differently from relapsing-remitting multiple sclerosis (RRMS) a group of patients present aquaporin-4 (AQP4) antibodies in the serum. Although its pathogenesis is unclear, cytokine profiles may impact disease activity and severity. Objective: To analyze cerebrospinal fluid (CSF) cytokine levels in NMOSD AQP4 + and their relationship with neurological disability, comparing findings with RRMS patients and non-inflammatory controls (NIC). Methods: Sixty-four participants were recruited: 11 NMOSD AQP4+, 29 RRMS, and 24 NIC. CSF cytokine levels were measured using a multiplex assay. Group comparisons were performed with Kruskal-Wallis and Mann-Whitney U tests, while linear regression models evaluated the association between cytokine levels and Expanded Disability Status Scale (EDSS) scores. Results: NMOSD AQP4 + patients displayed significantly higher CSF levels of IL-1β (p = 0.040), TNF-α (p < 0.001), G-CSF (p = 0.003), Eotaxin (p = 0.008), and MIP-1α (p = 0.005) compared to RRMS and NIC. Moreover, IL-1β CSF levels were positively associated with disability at the time of lumbar puncture (β = 22.24, SE = 7.73, p = 0.018), a relationship that remained significant after adjusting for age (β = 18.96, SE = 6.33, p = 0.040). Conclusions: Expression of proinflammatory cytokines may differ between NMOSD and RRMS. Elevated IL-1β levels in NMOSD AQP4 + patients are associated with neurological disability, suggesting a potential role as a biomarker of disease severity. Further studies are needed to confirm these findings and evaluate the therapeutic potential of targeting IL-1β in NMOSD.