Researchers Identify Testosterone-triggered Molecule that Protects Men from MS

A molecule triggered by the male hormone testosterone protects male mice from developing multiple sclerosis, Northwestern Medicine researchers report.

Their discovery may help explain why MS affects more women than men. It could also lead to targeted therapies to protect women against the disease.

The study, “Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility,” appeared in the journal Proceedings of the National Academy of Sciences.

The incidence of MS is three to four times higher in women than in men. Sex also determines the age at which the disease strikes and the course it takes.

Scientists knew these differences stemmed from the much higher testosterone levels in men, but they didn’t know the mechanism that caused the difference.

A research team led by Melissa Brown, a microbiology and immunology professor at Northwestern University’s Feinberg School of Medicine, used mice models of MS to explore the subject.

They found that, in male mice, testosterone could prompt immune cells called mast cells to produce the signaling molecule interleukin-33, or IL-33. The molecule promoted a cascade of cell signals that prevented the activation of inflammation-generating Th17 immune cells. Th17 cells play a key role in the destruction of nerve cells’ protective myelin layer — a hallmark of MS.

To further demonstrate IL-33’s nerve-cell-protective effect, the team blocked the activity of the molecule in male mice. This led to their MS symptoms quickly worsening.

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