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. 2013 Sep 19;8(9):e75021.
doi: 10.1371/journal.pone.0075021. eCollection 2013.

Inflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activity

Trygve Holmøy  1 , Kristin Ingeleiv Løken-Amsrud, Søren Jacob Bakke, Antonie G Beiske, Kristian S Bjerve, Harald Hovdal, Finn Lilleås, Rune Midgard, Tom Pedersen, Jutrate Saltytė Benth, Oivind Torkildsen, Stig Wergeland, Kjell-Morten Myhr, Annika E Michelsen, Pål Aukrust, Thor Ueland
Affiliations

Inflammation markers in multiple sclerosis: CXCL16 reflects and may also predict disease activity

Trygve Holmøy et al. PLoS One. .

Abstract

Background: Serum 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.

Methods: We 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.

Results: After 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.

Conclusions: Serum 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.

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Conflict of interest statement

Competing Interests: FL is employed by Curato Oslo and Tom Pedersen by Unilabs. The study was partly supported by Merck-Serono, Pronova Biocare and Bayer Schering. KILA has received travel support and an unrestricted research grant from Biogen Idec and travel support from Merck Serono. KMM has received honoraria for lecturing, participation in pharmaceutical company sponsored clinical trials, and travel support from Bayer Schering, Biogen Idec, Novartis, Merck-Serono and Sanofi Aventis. HH has participated in pharmaceutical company sponsored clinical trials and received travel support from Merck Serono, Biogen Idec and Bayer Schering. RM has received honoraria for lecturing, participation in pharmaceutical company sponsored clinical trials, and travel support from Bayer Schering, Biogen Idec, Novartis, Merck-Serono and Sanofi Aventis. SW has received speaker honoraria and travel support from Sanofi Aventis, Biogen Idec, Bayer Schering and Novartis. TH has received speaker honoraria and travel support from Sanofi Aventis, Biogen Idec, Bayer Schering, Novartis and Merck Serono. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. MRI activity and mean concentrations (positive SD) of inflammation markers significantly associated with MRI outcomes throughout the study.
All available observations at each time point are included (see Table S1 for numbers). All T1Gd+ lesions are shown at month 0 (baseline). Abbreviations: CXCL16: Chemokine (C-X-C motif) ligand 16, OPG: osteoprotegerin, MMP-9: matrix metalloproteinase 9, T1Gd+: gadolinium enhancing T1 MRI lesion, CUA: combined unique activity.
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