Scientists have discovered why men get dental disease more often and with greater severity than women, by pinpointing the specific inflammation that causes 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 an inflammatory protein, interleukin-1 beta (IL-1β), that increases activity in periodontitis in men, amplifying symptoms of the disease that contributes to tooth loss as it progresses. While we know that men are disproportionately affected by this dental disease, studies have done focused heavily on male behavior – such as poor oral hygiene or fewer visits to the dentist – as the reason they are more prone to the condition. While poor brushing and flossing habits can lead to the onset of periodontitis, it is the body’s inflammatory response that worsens symptoms over time.
Interleukins (IL) are a group of cytokines that play key roles in the activation and differentiation of immune cells and 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 diseases including glaucoma and age-related macular degeneration.
Analyzing 6,200 human samples in three studies, scientists found that men have significantly higher levels of IL-1β in the fluid found in the gingival crevice—a V-shaped area between the gums and each tooth. This activity can make gum and bone loss more pronounced when infection occurs.
“Our paradigm-shifting work not only identifies the inflammasome as a causative agent of male-biased periodontitis, but also points a clear path to developing gender-stratified treatments in periodontics,” said Julie Marchesan, of the UNC Adams School of Dentistry. “Prior to this work, the inflammasome was thought to have the same role in the development of inflammatory conditions in both women and men.”
In a mouse model, the researchers found that male animals had significantly higher IL-1β secretion than female rodents, mirroring what is seen in humans. Mice bred with inflammatory gene deletions showed 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 the infiltration of inflammatory cells into the 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 in suppressing the inflammatory response that leads to bone and gum loss. Ovariectomized female mice showed no change, further indicating that the male reproductive system is intrinsically linked to this particular immune system behavior.
“We found that inflammation-induced interleukin-1beta (IL-1β) represents a sex-dependent mechanism in three human data sets, which is mechanistically verified in mouse studies,” the researchers wrote. “Furthermore, targeting the inflammasome moderates racial bone resorption in the periodontium.”
While not yet proven in the human mouth, suppression of IL-1β shows great potential. The discovery paves the way not only for gender-specific research into the mechanisms underlying inflammatory diseases, but also for the development of therapies targeting the inflammatory body that could help prevent the progression of periodontitis. It could also help scientists understand how the disease progresses in female biology if it is not due to IL-1β activity.
According to the Centers for Disease Control and Prevention (CDC), two in five US adults age 30 and older have some degree of periodontitis, with about one in two men having it compared to one in three women. It is estimated that 60% of people over the age of 65 experience it.
“Our findings will enhance the development of therapies that target the inflammatory body and may specifically benefit male patients, while also paving the way for the discovery of biological mechanisms responsible for periodontitis in women,” added Marchesan.
The research was published in the journal Proceedings of the National Academy of Sciences.
Source: University of North Carolina at Chapel Hill via EurekAlert!
