Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction.

Haematologica 2020 Aug 28;105(8):2056-2070. Epub 2019 Nov 28.

Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

Chronic inflammation is a key pathological hallmark of multiple sclerosis (MS) and suggests that resolution of inflammation, orchestrated by specialized pro-resolving lipid mediators (LM), is impaired. Here, through targeted-metabololipidomics in peripheral blood of patients with MS, we revealed that each disease form was associated with distinct LM profiles that significantly correlated with disease severity. In particular, relapsing and progressive MS patients were associated with high eicosanoids levels, whereas the majority of pro-resolving LM were significantly reduced or below limits of detection and correlated with disease progression. Furthermore, we found impaired expression of several pro-resolving LM biosynthetic enzymes and receptors in blood-derived leukocytes of MS patients. Mechanistically, differentially expressed mediators like LXA, LXB, RvD1 and PD1 reduced MS-derived monocyte activation and cytokine production, and inhibited inflammation-induced blood-brain barrier dysfunction and monocyte transendothelial migration. Altogether, these findings reveal peripheral defects in the resolution pathway in MS, suggesting pro-resolving LM as novel diagnostic biomarkers and potentially safe therapeutics.

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2019.219519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395264PMC
August 2020

Publication Analysis

Top Keywords

blood patients
8
multiple sclerosis
8
blood-brain barrier
8
correlated disease
8
peripheral blood
8
barrier dysfunction
8
lipid mediators
8
specialized pro-resolving
8
pro-resolving lipid
8
reveal peripheral
4
eicosanoids levels
4
high eicosanoids
4
pd1 reduced
4
associated high
4
levels majority
4
majority pro-resolving
4
rvd1 pd1
4
reduced limits
4
findings reveal
4
pro-resolving reduced
4

Similar Publications