Scientists have discovered why males get dental disease more frequently and with greater severity than females, pinpointing the specific inflammation driving it. This could help treat gum and tooth decay in both sexes through different interventions.
Researchers at the University of North Carolina at Chapel Hill (UNC-Chapel Hill) have identified one inflammatory protein, interleukin-1 beta (IL-1β), ramps up activity in periodontitis in males, amplifying symptoms of the disease that contributes to tooth loss as it progresses. While we've known that men are disproportionately affected by this dental disease, studies have largely focused on male behavior – such as poorer oral hygiene or fewer dentist visits – as the reason they're more susceptible to the condition. While poor brushing and flossing habits can lead to the onset of periodontitis, the body's inflammation response is what worsens symptoms over time.
Interleukins (IL) are a group of cytokines that play key roles in activating and differentiating immune cells, and they have pro-inflammatory and anti-inflammatory properties. IL-1β is involved in mediating neuroinflammation and has been implicated in stroke, Alzheimer's disease and multiple sclerosis, as well as eye disease including glaucoma and age-related macular degeneration.
Analyzing 6,200 human samples across three studies, the scientists found that men have significantly higher IL-1β levels in the fluid that's found in the gingival crevice – a V-shaped area between gum and each tooth. This activity may make gum and bone loss more pronounced when infection occurs.
“Our paradigm-shifting work not only pinpoints the inflammasome as a causal driver of male-biased periodontitis but also demonstrates a clear path for the development of sex-stratified therapeutics in periodontics,” said Julie Marchesan, from the UNC Adams School of Dentistry. “Prior to this work, the inflammasome was believed to have the same role in the development of inflammatory conditions in both females and males."
In a mouse model, the researchers found that male animals had significantly higher IL-1β secretion than female rodents, mirroring what's seen in humans. Mice bred with inflammasome gene deletions experienced less bone loss in dental disease, and animals treated with the experimental caspase-1/4 inhibitor drug – which blocked the body's natural IL-1β response – had a significant reduction in inflammatory cells infiltrating into tissue.
This, however, was only seen in male mice – and when the scientists removed the testes, the caspase-1/4 inhibitor was no longer effective at suppressing the inflammatory response leading to bone and gum loss. Female mice with ovaries removed showed no change, further indicating that the male reproductive system is intrinsically linked to this specific immune system behavior.
"We found that inflammasome-induced interleukin-1 beta (IL-1β) represents a mechanism of sex dependency in three human datasets, which is verified mechanistically in murine studies," the researchers wrote. "Furthermore, targeting the inflammasome mitigates sex-biased bone resorption in the periodontium."
While it's yet to be demonstrated in human mouths, the suppression of IL-1β shows great potential. The discovery paves the way not just for sex-specific research into the mechanisms underlying inflammatory diseases, but also for the development of inflammasome-targeted treatments that could help prevent periodontitis progression. It could also help scientists understand how the disease advances in female biology, if it's not driven by IL-1β activity.
According to the Centers for Disease Control and Prevention (CDC), two in five US adults aged 30 years or older have some degree of periodontitis, with about one in two men suffering from it compared with one in three women. It's estimated that 60% of people over the age of 65 years experience it.
"Our findings will foster the development of therapies that target the inflammasome and can specifically benefit male patients, while also paving the way for the discovery of biological mechanisms responsible for periodontitis in females," Marchesan added.
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: University of North Carolina at Chapel Hill via EurekAlert!
