Clinical Significance of the Interleukin 6 in Neuromyelitis Optica Spectrum Disorder: A Systematic Review with Meta-analysis
Gerardo Luna-Peralta1, Alvaro Milla-Martinez2, Ivan Alegre-Cordero2, María Valvas-Acero2, Leonardo Di Cosmo3, Sarah Quiroz Patilla2, Carlos Daniel Torres-Palma2, Fabiola Cruces-Abarca2, Danielle Kei Pua4
1Universidad Nacional Mayor de San Marcos, Lima, Perú, 2Sociedad Científica de San Fernando, Universidad Nacional Mayor de San Marcos, Lima, Perú, 3Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy, 4Westchester Medical Center, New York, USA
Objective:

To summarize the current evidence on the clinical significance of interleukin (IL)-6 on neuromyelitis optica spectrum disorder (NMOSD).

Background:

Th17 cells and their cytokines, especially IL-6, play a key role in NMOSD pathogenesis. IL-6 is under investigation as a biomarker for disease activity, disability, and differential diagnosis.

Design/Methods:

We searched five databases (PubMed, Embase, Scopus, Web of Science and Google Scholar) up to March 2025 for observational studies on IL-6 and NMOSD. Random-effects meta-analyses were conducted when possible. Risk of bias was assessed with the Newcastle-Ottawa scale.

Results:

Sixteen studies (1044 patients) were included. Plasma IL-6 (pg/mL) levels were higher in NMOSD than in healthy-controls (MD = 6.1; 95% CI 1.34–10.86; I²=97.8%), as well as in the CSF (MD = 12.58 pg/mL; 95% CI –3.29 to 28.46; I²=69.8%). Compared with MS, IL-6 was slightly higher in serum (MD = 0.74; 95% CI –1.33 to 2.82; I²=38.1%) and CSF (MD = 11.96; 95% CI –11.58 to 35.51; I²=93%). Compared with MOGAD, IL-6 levels were higher in serum among NMOSD patients (MD = 0.58; 95% CI: 0.01 to 1.14; I² =0%), whereas no significant difference was found in CSF (MD = –181.65; 95% CI: –945.44 to 582.25; I²=36%). Among NMOSD patients, one study reported significantly higher IL-6 levels in AQP4+ vs AQP4–, both in serum (MD = 37.00; 95% CI: 31.13 to 42.87) and CSF (MD = 742.00; 95% CI: 623.96 to 860.04). All studies showed low to moderate risk of bias.

Conclusions:

IL-6 levels are elevated in both the serum and CSF of NMOSD patients compared to healthy controls, suggesting its potential as a biomarker. Differences with MS were small and uncertain, while comparisons with MOGAD showed discriminatory potential in serum. Further high-quality studies are needed to clarify its diagnostic value and establish reliable cut-off points.

10.1212/WNL.0000000000217869
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