TY - JOUR AU - Gijs Kooij*, AU - Claudio Derada Troletti*, AU - Alessandro Leuti, AU - Paul C. Norris, AU - Ian Riley, AU - Maria Albanese, AU - Serena Ruggieri, AU - Stephania Libreros, AU - Susanne M.A. van der Pol, AU - Bert van het Hof, AU - YoĆ«lle Schell, AU - Gisella Guerrera, AU - Fabio Buttari, AU - Nicola Biagio Mercuri, AU - Diego Centonze, AU - Claudio Gasperini, AU - Luca Battistini, AU - Helga E. de Vries, AU - Charles N. Serhan#, AU - Valerio ChiurchiĆ¹#, PY - 2020/08/01 Y2 - 2024/03/28 TI - Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction JF - Haematologica JA - haematol VL - 105 IS - 8 SE - Articles DO - 10.3324/haematol.2019.219519 UR - https://haematologica.org/article/view/9980 SP - 2056-2070 AB - 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 LXA4, LXB4, 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. ER -