New research recently published in the Proceedings of the National Academy of Science has uncovered an important difference in a critical immune system molecule, IL-33, in men and women, which could help to explain sex differences in MS.

Being able to identify the factor, or factors, involved in the sex differences of MS is very important, as it may reveal more information about the triggers and biological processes that drive MS. Ultimately, it may reveal ways that we can prevent or better treat both men and women with MS.

Gender differences

There are marked differences in how the immune system responds to infections in men and women. In many cases, infections can cause more severe illness in men than women. However, women are more likely to suffer from an autoimmune disease; approximately 70% of people with an autoimmune disease are female.

When it comes to MS, at least twice as many women live with MS than men. However, men with MS are, on average, older at diagnosis and are more likely to develop progressive disease than women.

Many factors that could cause this difference have previously been suggested, such as changes induced by the sex hormones, different genes found on the female sex chromosomes and even differences in bacterial species in women.


In this new study, the researchers focused on the immune system molecule IL-33, also known as interleukin-33L – a chemical that helps cells of the immune system to signal or ‘talk’ to one another.

The immune system is made up of many different types of cells which need to act in a coordinated way to fight off bacteria, viruses and other foreign bodies. One of the ways the immune system does this is by sending out chemical messages. This signalling needs to be tightly controlled, so that the right parts of the immune system can respond quickly and to an appropriate level, but also so that they can be switched off when the threat has been dealt with. IL­-33 is one of the messages that controls these switches.

In this study, the scientists investigated animals with an MS-like disease and tried to identify which parts of the immune system were responding and whether results differed between male and female animals. They also tried to decode the chemical signals being sent around the body and which cells were producing the signals.

Results showed that, in males, the type of immune response was different to that seen in females. The immune system appeared to be responding with what is known as a Th2 immune response – the sort of response the body typically switches on when infected with potential parasites. However, females predominantly had a Th17 immune response, which is normally associated with fighting other more general infections.

In the process of tracing back through the types of cells and molecules that were observed in these two types of responses, the researchers found a key difference in the level of IL-33 and discovered which cell was producing the different IL-33 response. Upon growing these cells in the lab and applying different amounts of testosterone to them, the team found that male cells responded by producing more IL-33, whereas the female cells didn’t respond at all.


These results could help to explain why women are more likely to switch on an autoimmune type immune response than men. It also may help explain why, as men age, their susceptibility to developing MS increases as their levels of testosterone fall.

Studies like this may open avenues to discovering new treatments. Testosterone itself may not be a suitable therapy, especially for females, given its wide-ranging effects on the body. But, since IL-33 is involved in ‘translating’ the message that testosterone delivers to the immune system, IL-33 could provide a more precise tool to influence the immune system to treat MS.

With thanks to MS Research Australia – the lead provider of research summaries on our website.