IL-6 in the Cerebrospinal Fluid Signals Disease Activity in Multiple Sclerosis

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.

A STAT3 inhibitor ameliorates CNS autoimmunity by restoring Teff:Treg Balance

“…Phosphorylated STAT3 (pSTAT3) was significantly higher in CD4 + T cells from relapsing-remitting MS (RRMS) patients in relapse compared with those in remission and healthy controls (HCs) ( 20 ). IL-6 level is higher in the cerebrospinal fluid (CSF) of MS patients compared with HCs ( 21 , 22 ). IL-6 receptor (IL-6R) level is significantly higher in CD4 + T cells of MS patients than HCs ( 18 , 23 ).…”

The Unfolded Protein Response in Immune Cells as an Emerging Regulator of Neuroinflammation

“…From an inflammatory perspective, increased levels of IL-6, TNF, and IL-1β are detected in the brain, cerebrospinal fluid, and serum of patients with AD, PD, and MS, although these responses have not been yet linked to IRE1 or PERK activation (Swardfager et al, 2010;Qin et al, 2016;Chen X. et al, 2018;Stampanoni Bassi et al, 2020). Analogous to peripheral macrophages, microglia initiate inflammation upon recognition of Aβ, α-syn, and neuromelanin through TLR2 and TLR4 (Reed-Geaghan et al, 2009;Zhang et al, 2011;Kim et al, 2013).…”

Th17-Related Cytokines as Potential Discriminatory Markers between Neuromyelitis Optica (Devic’s Disease) and Multiple Sclerosis—A Review

“…The optimal cut-off CSF IL-6 point has been found as 7.8 pg/mL for diagnosing NMO [135]. On the other hand, it has been suggested that IL-6 is a candidate for a rather non-specific prognostic biomarker as elevated levels of this cytokine are also associated with neuroinflammatory diseases other than NMO [137].…”