Increased Apolipoprotein A-I levels improve clinical and biological markers in EAE

Background: Apolipoprotein A-I (ApoA-I) is the lipid of highest concentration in the cholesterol molecule and has been shown to have anti-inflammatory properties. It is also overexpressed in the brain and spinal cord. Recent studies revealed that progressive MS patients have lower serum levels of ApoA-I compared to healthy individuals or relapsing remitting MS patients (Meyers et al., 2014, Journal of Neuroimmunology 277, pp176-185). 

Objectives: We hypothesized that ApoA-I levels might cause clinical and biological changes in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. Our objective was to investigate if variation in ApoA-I levels could alter disease progression.

Methods: ApoA1 deficient female mice (C57Bl/6-Tg(ApoA1)1Rub/J)  demonstrated a higher incidence and severity of the EAE in comparison to the wild type control mice (C57Bl/6J). EAE was accompanied by an increase in cytokines (INF-g, TNF-a, TGF-ß, IL-2, IL-23) and T-cell differentiation into CD25+/Foxp3+ T-cells. Because ApoA-I levels can be modulated by liver X receptors (LXRs), we next tested whether the LXR agonist GW3965 and fenofibrate (a downregulator of ApoA-I in mice) altered EAE.

Results:  We found that mice treated with the oral agent GW3965 had a lower disease incidence, EAE scores and cytokine expression compared to mice with standard EAE or animals treated with fenofibrate. Variation of ApoA-I levels correlated with disease incidence and severity. Further, GW3965 supplementation resulted in increased ApoA-I production in the liver and in the spinal cord of experimental animals.

Conclusions: These data suggest that ApoA-I is a novel target for immune modulation by an oral medication, which might be applicable to MS patients.