Netrin-1 and multiple sclerosis: a new biomarker for neuroinflammation?

Background and purpose Netrin-1, an axon guidance protein, reduces serum levels of pro-inflammatory mediators and stabilizes the blood−brain barrier limiting the entrance of immune cells into the central nervous system. The aim was to investigate its presence in the experimental autoimmune encephalomyelitis ( EAE) model and in multiple sclerosis ( MS) patients with and without clinical activity. Methods Netrin-1 levels were evaluated in EAE mouse tissues. Afterwards, serum netrin-1 was cross-sectionally quantified in 90 patients with different MS phenotypes and 30 control subjects. An additional group of 10 relapsing−remitting MS ( RRMS) patients was longitudinally evaluated throughout a relapse ( RRMSr) with an interval of 60 days. Tumour necrosis factor α ( TNFα), a reference inflammatory cytokine, and netrin-1 were quantified by enzyme-linked immunosorbent assay. Results Experimental autoimmune encephalomyelitis mice showed significantly lower netrin-1 levels and higher TNFα amounts in sera, spinal cord and cerebella than healthy control mice. MS patients showed significantly lower serum netrin-1 levels than controls (511.62 ± 209.30 and 748.32 ± 103.24 pg/ml, respectively; P ≤ 0.005). The lowest protein levels were found in RRMSr, remaining significantly lower throughout the relapse. TNFα serum concentrations were higher in MS patients compared to controls, and negatively correlated with netrin-1 levels ( r = −0.3734, P ≤ 0.0001). Conclusions Netrin-1 decreased in EAE and in MS patients, mainly during relapse, suggesting an anti-inflammatory role of netrin-1. Further research should be performed in a larger cohort of patients to validate netrin-1 as a biomarker of MS inflammatory activity. [ABSTRACT FROM AUTHOR]