Cerebrospinal fluid detection of interleukin-1beta in phase of remission predicts disease progression in multiple sclerosis

BACKGROUND: Absence of clinical and radiological activity in relapsing-remitting multiple sclerosis (RRMS) is perceived as disease remission. We explored the role of persisting inflammation during remission in disease evolution. METHODS: Cerebrospinal fluid (CSF) levels of interleukin 1beta (IL-1beta), a major proinflammatory cytokine, were measured in 170 RRMS patients at the time of clinical and radiological remission. These patients were then followed up for at least 4 years, and clinical, magnetic resonance imaging (MRI) and optical coherence tomography (OCT) measures of disease progression were recorded. RESULTS: Median follow-up of RRMS patients was 5 years. Detection of CSF IL-1beta levels at the time of remission did not predict earlier relapse or new MRI lesion formation. Detection of IL-1beta in the CSF was instead associated with higher progression index (PI) and Multiple Sclerosis Severity Scale (MSSS) scores at follow-up, and the number of patients with sustained Expanded Disability Status Scale (EDSS) or Multiple Sclerosis Functional Composite worsening at follow-up was higher in individuals with detectable levels of IL-1beta. Patients with undetectable IL-1beta in the CSF had significantly lower PI and MSSS scores and a higher probability of having a benign MS phenotype. Furthermore, patients with undetectable CSF levels of IL-1beta had less retinal nerve fiber layer thickness and macular volume alterations visualized by OCT compared to patients with detectable IL-1beta. CONCLUSIONS: Our results suggest that persistence of a proinflammatory environment in RRMS patients during clinical and radiological remission influences midterm disease progression. Detection of IL-1beta in the CSF at the time of remission appears to be a potential negative prognostic factor in RRMS patients.