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 aqua-porin-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-1 beta (p = 0.040), TNF-alpha (p < 0.001), G-CSF (p = 0.003), Eotaxin (p = 0.008), and MIP-1 alpha (p = 0.005) compared to RRMS and NIC. Moreover, IL-1 beta CSF levels were positively associated with disability at the time of lumbar puncture (beta = 22.24, SE = 7.73, p = 0.018), a relationship that remained significant after adjusting for age (beta = 18.96, SE = 6.33, p = 0.040). Conclusions Expression of proinflammatory cytokines may differ between NMOSD and RRMS. Elevated IL-1 beta 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-1 beta in NMOSD. Highlights circle NMOSD AQP4 + patients show distinct cytokine profiles compared to RRMS and NIC. circle Elevated IL-1 beta levels are associated with disability in NMOSD AQP4 + patients. circle IL-1 beta could serve as a potential biomarker and therapeutic target in NMOSD