Possible Mechanism for Protective Effect of Testosterone in Multiple Sclerosis Uncovered

Highlights:

• Testosterone has a protective effect against multiple sclerosis, a chronic condition that affects nerves.
• The benefit appears to be due to the stimulation of the production of interleukin-33 by mast cells.
• The discovery opens up new options for the development of treatments for multiple sclerosis.

The male hormone testosterone stimulates the release of a molecule called interleukin 33 (IL-33), which could protect women from multiple sclerosis. The study in mice which revealed this finding was published in the Proceedings of the National Academy of Sciences. Multiple sclerosis affects females around three-to-four times more commonly as compared with males. It also manifests at an earlier age in females as compared to males.

Following their experiments in mice, the scientists proposed a possible mechanism for the protective effect of testosterone in multiple sclerosis. Multiple sclerosis arises when a type of immune cells called Th17 cells damage the myelin sheath that covers the nerves. The male hormone testosterone stimulates the release of a molecule called IL-33 by certain immune cells called the mast cells (which often mediate an allergic reaction). IL-33 in turn stimulates multiple reactions that ultimately prevent the development of the Th17 cells, and reverses changes associated with multiple sclerosis in female mice.

The findings of this study could possibly explain the reason behind the fact that males are less likely to suffer from multiple sclerosis as compared to females. Additional research focused on these findings will hopefully provide an additional treatment option for patients with the debilitating disease. Though women may not have the natural benefit of testosterone in preventing multiple sclerosis and cannot be directly administered testosterone due to its side effects, a new treatment can be developed that uses the testosterone and IL-33 mediated pathway to protect females from the disease.

About Multiple Sclerosis

Multiple sclerosis is an autoimmune condition where antibodies attack the myelin sheath, the membrane that encases nerves in the brain and the spinal cord. Damage to the sheath disrupts the function of the nerves, resulting in progressive weakness, sensory loss and cognitive defects, sometimes even crippling the patient.

Treatment of multiple sclerosis currently consists of medicines to modify the course of the disease like beta interferon, glatiramer, natalizumab and mitoxantrone hydrochloride, drugs that relieve symptoms that include corticosteroids, muscle relaxants, antidepressants and gabapentin, and physical and occupational therapy to cope with disability caused by the disease.

Reference:

1. Abigail E. Russi, Mark E. Ebel, Yuchen Yang and Melissa A. Brown. Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility. PNAS (2018); https://doi.org/10.1073/pnas.1710401115

Source-Medindia