Abstract
Specific proinflammatory and anti-inflammatory molecules could represent useful cerebrospinal fluid (CSF) biomarkers to predict the clinical course of multiple sclerosis (MS). The proinflammatory molecule interleukin (IL)-6 has been investigated in the pathophysiology of MS and has been associated in previous smaller studies to increased disability and disease activity. Here, we wanted to further address IL-6 as a possible CSF biomarker of MS by investigating its detectability in a large cohort of 534 MS patients and in 103 individuals with other non-inflammatory neurological diseases. In these newly diagnosed patients, we also explored correlations between IL-6 detectability, MS phenotypes, and disease characteristics. We found that IL-6 was more frequently detectable in the CSF of MS patients compared with their control counterparts as significant differences emerged between patients with Clinically isolated syndrome (CIS), Relapsing–remitting (RR), and secondary progressive and primary progressive MS compared to non-inflammatory controls. IL-6 was equally present in the CSF of all MS phenotypes. In RR MS patients, IL-6 detectability was found to signal clinically and/or radiologically defined disease activity, among all other clinical characteristics. Our results add further evidence that CSF proinflammatory cytokines could be useful for the identification of those MS patients who are prone to increased disease activity. In particular, IL-6 could represent an interesting prognostic biomarker of MS, as also demonstrated in other diseases where CSF IL-6 was found to identify patients with worse disease severity.
Highlights
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by a highly variable clinical course
The analysis of the distribution of patients with various MS phenotypes and of control subjects, according to cerebrospinal fluid (CSF) IL-6 detectability, demonstrated that IL-6 was more frequently present in Clinically isolated syndrome (CIS) patients in comparison to controls [90/98 (91.8%) vs. 71/103 (68.9%), p = 0.001], RR-MS patients vs. controls [281/329 (85.4%) vs. 71/103 (68.9%), p = 0.001], SP-MS patients vs. controls [20/21 (95.2%) vs. 71/103 (69.7%), p = 0.013], and PP-MS [34/39 (87.2%) vs. 71/103 (68.9%), p = 0.027], respectively
IL-6 is a classic cytokine featuring pleiotropic functions and that mediates a number of biological activities, including immune response regulation
Summary
Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by a highly variable clinical course. Experimental studies showed that proinflammatory molecules alter neuronal functioning by promoting excitotoxic neurodegeneration. These observations have highlighted that neuroinflammation may represent an independent and an important cause of neurodegeneration since the early phases of MS. Anti-inflammatory molecules could reduce the immune damage of the CNS, modulating the immune response and exerting a beneficial effect on MS course, promoting neuroprotection (Cheng and Mattson, 1995; Lobo-Silva et al, 2016)
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