Inflammation Markers in Multiple Sclerosis: CXCL16 Reflects and May Also Predict Disease Activity

Abstract

BackgroundSerum markers of inflammation are candidate biomarkers in multiple sclerosis (MS). ω-3 fatty acids are suggested to have anti-inflammatory properties that might be beneficial in MS. We aimed to explore the relationship between serum levels of inflammation markers and MRI activity in patients with relapsing remitting MS, as well as the effect of ω-3 fatty acids on these markers.MethodsWe performed a prospective cohort study in 85 relapsing remitting MS patients who participated in a randomized clinical trial of ω-3 fatty acids versus placebo (the OFAMS study). During a period of 24 months 12 repeated magnetic resonance imaging (MRI) scans and nine serum samples were obtained. We measured 10 inflammation markers, including general down-stream markers of inflammation, specific markers of up-stream inflammatory pathways, endothelial action, and matrix regulation.ResultsAfter Bonferroni correction, increasing serum levels of CXCL16 and osteoprotegerin were associated with low odds ratio for simultaneous MRI activity, whereas a positive association was observed for matrix metalloproteinase (MMP) 9. CXCL16 were also associated with low MRI activity the next month, but this was not significant after Bonferroni correction. In agreement with previously reported MRI and clinical results, ω-3 fatty acid treatment did not induce any change in the inflammation markers.ConclusionsSerum levels of CXCL16, MMP-9, and osteoprotegerin reflect disease activity in MS, but are not affected by ω-3 fatty acid treatment. CXCL16 could be a novel biomarker and potential predictor of disease activity in MS.

Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis

“…The use of immunomodulatory therapy, which mostly comprised IFN-b treatment, had some effect on the systemic inflammation markers examined. This supports our previous findings of an increase of CXCL16 and IL-1Ra after initiation of IFN-b therapy [12], and suggests that immunomodulatory treatment can induce favorable alterations in the patient's inflammatory profile. CXCL16 and IL-1Ra have been implicated in protective processes in the central nervous system with CXCL16 reducing damage secondary to increased glutamate levels and decreased oxygen and glucose levels, and IL-1Ra counteracting the widespread pro-inflammatory effects of IL-1 signaling through type I IL-1 receptors [33,34].…”

“…25(OH)D levels were measured by mass spectroscopy (Applied Biosystems/MDS Sciex, Foster City, CA, USA) and inflammation marker concentrations were determined with enzyme immunoassay kits (R&D Systems, Stillwater, MN, USA), as previously described [12,19]. 68 patients were included in the final analyses, as four patients were excluded due to only providing baseline measurements.…”

“…Additional adjustments were made for change in use of immunomodulatory treatment during the study, as this may alter the concentration of the inflammation markers [12]. Finally, correction for high vitamin D intake and UVR exposure prior to study initiation was included, as both were associated with high baseline 25(OH)D levels (data not shown), and UVR may independently affect inflammatory process in RRMS [20,21].…”

“…Given the previously recorded associated effects of IFN-b treatment on the inflammation markers [12], we anticipated differences between patients with and without immunomodulatory treatment in this study as well. In line with our earlier results, significantly higher mean baseline levels of IL-1Ra and CXCL16, together with a strong trend for lower baseline levels of MMP-9, were found among patients on compared to off immunomodulatory therapy (Table 3).…”

“…Of particular interest, we found that each * 25 nmol/L increase of serum 25(OH)D was associated with a *5-15 % increase of sFRP3 and IL-1Ra before initiation of interferon-b1a (IFN-b) treatment. Further, initiation of IFN-b therapy was associated with extensive alterations of most of the inflammation markers [12], but no synergistic effects between IFN-b treatment and patient 25(OH)D levels were observed on these markers [13]. However, as the observed rise in 25(OH)D levels was mainly driven by sun-induced vitamin D synthesis [13], the results attributed to increasing 25(OH)D may have been confounded by other immunomodulatory effects of ultraviolet radiation (UVR) [14][15][16].…”