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Background Longitudinally extensive transverse myelitis (LETM) is a severe inflammatory spinal cord disorder. It is commonly associated with neuromyelitis optica spectrum disorders and other autoimmune conditions like Sjögren syndrome, infectious and idiopathic aetiologies. Interleukin-6 (IL-6) is one of the key pro-inflammatory cytokines implicated in neuroinflammation and may serve as an important biomarker of disease activity.Objective To evaluate the correlation between cerebrospinal fluid (CSF) IL-6 levels and disease activity in patients with LETM and to assess its prognostic value for short-term functional outcomes.Methods In this prospective follow-up study conducted over 18 months, 41 patients with LETM and 21 controls with non-inflammatory neurological conditions were enrolled. Disease severity was assessed using the Expanded Disability Status Scale (EDSS) at admission and at 3-month follow-up. CSF IL-6 levels were analysed and correlated with clinical and radiological variables using Spearman correlation, receiver operating characteristic (ROC) analysis and multivariate regression.Results Median CSF IL-6 levels were significantly higher in LETM patients than controls (11.26 vs 5.02 pg/mL; p<0.001). CSF IL-6 showed a moderate positive correlation with EDSS at admission (ρ=0.34, p=0.027) and follow-up (ρ=0.51, p<0.001). ROC analysis demonstrated fair predictive accuracy for severe disease (AUC=0.70), with a cut-off of approximately 7 pg/mL. Multivariate analysis identified CSF IL-6 as an independent predictor of disease severity.Conclusions CSF IL-6 correlates with disease activity and disability in LETM and may serve as a useful biomarker for prognostication and treatment planning.