Pro-resolution lipid mediator maresin-1 reduces inflammation, promotes neuroprotection, and prevents disease progression in multiple sclerosis model of autoimmunity

Abstract ID: 474

Newswise — Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease in young adults, resulting in neurological defects and disability. The endogenous mechanisms for resolving inflammation are intact but become defective in patients, resulting in a lack of resolution mediators and unresolved inflammation. Because DHA metabolism is impaired in MS, we hypothesize that supplementing its downstream metabolite maresin 1 (MaR1) will alleviate inflammation and demyelination in animal model of MS called experimental allergic encephalomyelitis (EAE). EAE was induced in SJL mice, followed by treatment with MaR1 (300ng, 200ul in PBS/animal/day ip) on day 6 after disease induction. Monitoring the disease course, recall response by ELISA, cytokine expression analysis by qPCR and western blotting, and immune profiling by flow cytometry were used to assess the effect of MaR1 treatment in EAE. The neuroprotective effect of MaR1 was also assessed using single molecule array (SIMOA), histopathology, and IHC. Statistical analysis was done using Graph-Pad Prism. Restoration of MaR1 had a protective effect on neurological deficits, prevented disease progression, and reduced disease severity in EAE by reducing immune cell infiltration (CD4+IL17+ and CD4+IFN+) into the CNS (P<0.001). It significantly reduced the proinflammatory cytokine IL17 (P<0.01) and promoted an antiinflammatory response via IL10 and IL4 (P<0.001). Furthermore, it exerted neuroprotective effects as evidenced by higher MBP expression in the brain from the MaR1 treated group. Overall, MaR1 supplementation has anti-inflammatory and neuroprotective effects in preclinical animal models, implying that it could be a new therapeutic molecule in MS.