Testosterone would protect men against multiple sclerosis (MS), according to a recent scientific study, at least when they are young. This testosterone level, naturally 7 to 8 times higher in men than in women, would stimulate the production of IL-33, a protein of the inflammatory cascade of multiple sclerosis, which would have a protective effect against multiple sclerosis. A disabling and mysterious autoimmune disease for patients who hope for more effective and above all better tolerated drugs.
Multiple sclerosis is the 2e cause of handicap in young adults, just after road accidents. Given this frequency, research is extremely active. We recently know that it is an inflammatory disease probably due to a reaction of our organism to an external aggression – perhaps a virus – in people with a genetic predisposition.
Two women for one man
Eighty thousand people affected in France, two million in the world, with an originality, until today unexplained, two women affected for a man. Researchers at Northwestern University in the United States have discovered why men are less likely to develop multiple sclerosis than women. By identifying a molecule – the production of which is triggered by a high level of testosterone in the blood – they discovered that it helped protect them from disease.
During this study, published in PNAS, female mice genetically engineered to have an autoimmune brain disease like multiple sclerosis were treated with interleukin IL-33, a molecule believed to have a protective effect against the disease. The production of this interleukin IL-33 is induced by an elevated level of testosterone in the blood.
“This explains the lower risk in men of developing multiple sclerosis and other autoimmune diseases (lupus, rheumatoid arthritis, multiple sclerosis) compared to women, enthuses Melissa Brown, professor of microbiology at Northwestern University. These findings could lead to a new kind of treatment for MS, through interleukin IL-33 or the pathways it stimulates, and which we badly need. “
Testosterone as a bulwark
Indeed, women would be three to four times more likely to suffer from MS than men because their natural testosterone level is 7 to 8 times lower than in men. On the other hand, MS starts later in life in men, at an age when their testosterone levels start to drop. But until now, scientists haven’t figured out how testosterone can provide protection for men.
“This is why it is essential to study gender differences in research,” hammered Dr. Brown. Testosterone, given to men with MS, has had a positive influence on myelin destruction and nerve fiber degeneration, but this treatment is not possible in the long term. On the other hand, giving the IL-33 protein, the production of which is induced by testosterone, or stimulating the Th-2 type immunological response of the immune system by another route, would be possible.
A disease that attacks myelin
In multiple sclerosis, there is an imbalance in the immune system and the cells of this system, especially Th-17, attack the myelin sheath (the white matter that surrounds nerve cells or “neurons”).
Originally, this myelin sheath acts as an insulator and helps send nerve signals from the brain and spinal cord to the rest of the body. When the myelin sheath is damaged, normal conduction of the nerve signal is interrupted, which can lead to a variety of neurological symptoms, such as sensory disturbances, loss of motor function, and cognitive deficits.
A promising new molecule
Testosterone promotes the development of innate immune system cell formation, mast cells which in turn produce a protein that plays a key role in the inflammation cascade, the cytokine IL-33.
This in turn triggers the activation of an inflammatory protein cascade that prevents the overexpression of another type of immune cell, called Th17 cells, which can directly attack myelin. It is thanks to this mechanism of direct inhibition of Th-17 lymphocytes, via IL-33, that young men are better protected from multiple sclerosis than women.
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