IL-1β Levels During MS Remission May Predict Progression
A study of 170 patients with relapsing-remitting MS found that detectable levels of IL-1β in cerebrospinal fluid may help predict disease progression
Detection of interleukin-1β (IL-1β) in cerebrospinal fluid (CSF) during periods of remission appears to be a potentially negative prognostic factor in patients with relapsing-remitting multiple sclerosis (RRMS), according to findings from a new study.
Writing in the February 18 Journal of Neuroimmunology, Silvia Rossi, M.D., of the Multiple Sclerosis Clinical Centre, Tor Vergata Hospital, Rome, Italy, and colleagues noted that until recent years the absence of clinical and radiologic activity in RRMS had been considered evidence of remission (Rossi et al., 2014). However, with new diagnostic technologies—unconventional MRI along with others—it is now apparent that disease processes may be active even in asymptomatic patients.
Pathological studies have demonstrated that synapse, neuronal, and glial losses may occur in the absence of demyelination. In addition, even during relapses of MS, levels of IL-1β in CSF may be sufficiently high to trigger excitatory transmission and excitotoxic damage in neurons, the researchers wrote.
In an effort to find out more, these investigators measured CSF concentrations of IL-1β in 170 newly diagnosed RRMS patients during periods of remission, as assessed by standard clinical and radiological criteria. Upon diagnosis all patients had begun various disease-modifying therapies.
Using MRI, optical coherence tomography, and clinical assessment, the researchers followed the patients for a mean of 5 years.
They reported that although IL-1β levels in CSF measured during remission were correlated neither with earlier relapses nor with formation of new lesions, they were associated with higher progression indexes (PI) and Multiple Sclerosis Severity Scale (MSSS) scores at follow-up visits.
In addition, the researchers said, compared with patients who had undetectable levels of IL-1β (threshold of 0.56 pg/mL) during remission, those whose IL-1β levels were detectable had poorer sustained Expanded Disability Status Scale or Multiple Sclerosis Functional Composite scores at follow-up visits.
Patients with undetectable IL-1β had significantly lower PI and MSSS scores than did patients with detectable levels. They also were more likely to have benign MS phenotypes, the researchers reported.
Yet more evidence that IL-1β levels during remission make a difference: Patients whose levels were undetectable showed less ocular damage than that in patients with detectable levels.
"Our results suggest that persistence of a proinflammatory environment in RMSS patients during clinical and radiological remission influence midterm disease progression," the researchers conclude.
Key open questions
- Are the processes that affect normal-appearing tissue during remission in RRMS patients the result of "silent" inflammation, neurodegeneration, or both?
- Is tracking of IL-1β levels in the CSF of patients with RRMS a useful tool in predicting prognosis?
- Would lowering the detection threshold of the immunoassay used in this study (0.56 pg/mL) help to better identify patients who are progression-free?
- This study followed RRMS patients for a mean of 5 years. Would longer-term follow-up yield the same or similar results?
Disclosures and sources of funding
The present investigation was funded by a grant from Fondazione Italiana Sclerosi Multipla and by a grant from Ministero della Salute to DC. Some of the authors disclosed competing interests involving a variety of commercial entities including Almirall, Bayer Schering, Biogen Idec, Merck Serono, Novartis, Roche, Sanofi-Aventis, and Teva