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

Abstract

BackgroundAbsence 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.MethodsCerebrospinal fluid (CSF) levels of interleukin 1β (IL-1β), 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.ResultsMedian follow-up of RRMS patients was 5 years. Detection of CSF IL-1β levels at the time of remission did not predict earlier relapse or new MRI lesion formation. Detection of IL-1β 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-1β. Patients with undetectable IL-1β 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-1β had less retinal nerve fiber layer thickness and macular volume alterations visualized by OCT compared to patients with detectable IL-1β.ConclusionsOur results suggest that persistence of a proinflammatory environment in RRMS patients during clinical and radiological remission influences midterm disease progression. Detection of IL-1β in the CSF at the time of remission appears to be a potential negative prognostic factor in RRMS patients.

Multiple Sclerosis: Myeloperoxidase Immunoradiology Improves Detection of Acute and Chronic Disease in Experimental Model

“…In addition, detection of disease activity between relapses is crucial, because the number or severity of relapses does not correlate with disease progression (28). In contrast, persistent inflammation during clinical and radiologic remission correlates with disease progression (29), and inflammation in the normal-appearing white matter contributes more strongly to disability than the T2 lesion load (30,31). An imaging test that specifically assesses inflammatory disease activity would help to circumvent these problems.…”

T helper 9 cells induced by plasmacytoid dendritic cells regulate interleukin-17 in multiple sclerosis

“…The EDSS, evaluated every 6 months since diagnosis, was used in combination with disease duration to calculate two measures of disease severity, the progression index (PI) and the mean MS severity scale (MSSS). PI was defined as EDSS/disease duration [22]. The MSSS is an algorithm that relates EDSS scores to distribution of disability in patients with comparable disease durations [23].…”

“…Self-report and physician report were confirmed by record review. A subset of RR-MS patients (n = 88) without history of optic neuritis and ophthalmological disease underwent measurement of nerve fibre layer (RNFL) thickness and macular volume (MV) for both eyes using Stratus Optical Coherence Tomography (OCT) software version 4.0.2, Carl Zeiss Meditec, Inc. [22,24]. Briefly, for MV, retinal thickness was measured automatically as the distance between the vitreoretinal interface and the anterior boundary of the retinal pigment epithelium.…”

Hippocampal neuroplasticity and inflammation: relevance for multiple sclerosis

“…Thus, IL-1β could exert a fundamental role in modulating and favoring synaptic plasticity when expressed at physiological low levels, while an increased expression of this cytokine, such as during neuroinflammatory processes, could exert detrimental effects on neuroplasticity in the hippocampus. Interestingly, a recent study assessed the cerebro-spinal fluid (CSF) levels of this cytokine in 170 patients with relapsing-remitting MS, during clinical and radiological remission [73]. As result, higher CSF levels of IL-1β were found to be associated with midterm disease progression [73].…”

“…Interestingly, a recent study assessed the cerebro-spinal fluid (CSF) levels of this cytokine in 170 patients with relapsing-remitting MS, during clinical and radiological remission [73]. As result, higher CSF levels of IL-1β were found to be associated with midterm disease progression [73]. This work could support the hypothesis that an inflammatory environment in the CNS, potentially leading to the failure of brain plastic capacities, could play a pathogenic role during disease progression in patients with MS.…”