Summary: Administering a lipid that mediates inflammation reduced chronic inflammation associated with multiple sclerosis in mouse models. Researchers found these mediator lipids are reduced in humans with multiple sclerosis.
Source: UAB
A team led by the Institut de Neurociències at the Universitat Autònoma de Barcelona (INc-UAB) managed to reduce chronic inflammation associated with multiple sclerosis in mice thanks to the administration of a type of lipid that mediates inflammation.
The team found that these types of mediator substances, responsible for resolving the inflammatory process when it is no longer beneficial, are minimized in people with multiple sclerosis as well as in animal models of the disease.
The use of these mediators could become a good strategy for the treatment of this autoimmune disease.
Acute inflammation is a protective response to infection that promotes tissue regeneration after injury. Once its function has been performed, a series of mechanisms regulated by lipids acting as mediators are responsible for resolving it.
An error in the resolution response results in uncontrolled inflammation that is detrimental for the tissues.
In multiple sclerosis, an autoimmune disorder in which the body’s defense cells attack the lining of the tail of neurons (myelin), the inflammation is persistent and plays a key role in the development of the disease.
A research team led by Rubén López-Vales, Professor of Physiology at the UAB and researcher at the Neuroplasticity and Regeneration Group, INC-UAB, has managed to reduce the chronic inflammation associated with multiple sclerosis in a mice model of the disease, by administering one of the resolving lipid mediators of inflammation, Maresin-1.
The substance exerted a therapeutic effect on mice, drastically reducing the amount of proteins promoting inflammation (cytokines), as well as the number of cells in the immune system in both the spinal cord and the blood.
A continuous administration of the lipid over time also protected neurons from demyelination and improved the effects of neurological deterioration caused by the disease.
In the study, published in the Journal of Neuroinflammation, researchers looked at samples from patients with multiple sclerosis and from mice models, and found that there was insufficient production of Maresin-1 and other lipid mediators that end inflammation.
The levels of these immunosuppressive substances, which were almost undetectable, prevented the inflammatory process from stopping.
“Our results suggest that one of the body’s mechanisms for resolving inflammation is not working properly in patients with multiple sclerosis, which could partly explain the episodes of autoimmunity they experience”, says Dr. López-Vales.
The study, conducted in collaboration with the University of Montreal and the Universidad de La República in Uruguay, points to therapy with inflammatory-resolving mediators as an innovative and promising strategy for the treatment of multiple sclerosis and other autoimmune diseases needing further research.
Finally, López-Vales explains that the next steps will be a series of tests and experiments to demonstrate the safety of the administration of this lipid, which could allow them to address possible efficacy studies in humans.
About this multiple sclerosis research news
Author: Maria Jesus Delgado
Source: UAB
Contact: Maria Jesus Delgado – UAB
Image: The image is in the public domain
Original Research: Open access.
“Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis” by Rubén López-Vales et al. Journal of Neuroinflammation
Abstract
Administration of Maresin-1 ameliorates the physiopathology of experimental autoimmune encephalomyelitis
Background
Resolution of inflammation is an active and regulated process that leads to the clearance of cell debris and immune cells from the challenged tissue, facilitating the recovery of homeostasis. This physiological response is coordinated by endogenous bioactive lipids known as specialized pro-resolving mediators (SPMs). When resolution fails, inflammation becomes uncontrolled leading chronic inflammation and tissue damage, as occurs in multiple sclerosis (MS).
Methods
SPMs and the key biosynthetic enzymes involved in SPM production were analysed by metabololipidomics and qPCR in active brain lesions, serum and peripheral blood mononuclear cells (PBMC) of MS patients as well as in the spinal cord of mice with experimental autoimmune encephalomyelitis (EAE). We also tested the therapeutic actions of the SPM coined Maresin-1 (MaR1) in EAE mice and studied its impact on inflammation by doing luminex and flow cytometry analysis.
Results
We show that levels of MaR1 and other SPMs were below the limit of detection or not increased in the spinal cord of EAE mice, whereas the production of pro-inflammatory eicosanoids was induced during disease progression. Similarly, we reveal that SPMs were undetected in serum and active brain lesion samples of MS patients, which was linked to impaired expression of the enzymes involved in the biosynthetic pathways of SPMs.
We demonstrate that exogenous administration of MaR1 in EAE mice suppressed the protein levels of various pro-inflammatory cytokines and reduced immune cells counts in the spinal cord and blood.
MaR1 also decreased the numbers of Th1 cells but increased the accumulation of regulatory T cells and drove macrophage polarization towards an anti-inflammatory phenotype. Importantly, we provide clear evidence that administration of MaR1 in mice with clinical signs of EAE enhanced neurological outcomes and protected from demyelination.
Conclusions
This study reveals that there is an imbalance in the production of SPMs in MS patients and in EAE mice, and that increasing the bioavailability of SPMs, such as MaR1, minimizes inflammation and mediates therapeutic actions. Thus, these data suggest that immunoresolvent therapies, such as MaR1, could be a novel avenue for the treatment of MS.
