Sex hormones linked to asthma risk
US research finds gender and puberty strongly affect asthma risk in mice and humans. Jeff Glorfeld reports.
Women are twice as likely as men to have asthma, but before puberty the pattern is reversed, with boys the most common sufferers.
This gender-based difference may be caused by the effects of sex hormones on lung cells, according to a study published this week in the journal Cell Reports.
Researchers at Vanderbilt University and Johns Hopkins in the United States were surprised to finds that testosterone hindered an immune cell linked to asthma symptoms, such as inflammation and mucus production in the lungs.
"When we started this study, we really thought that ovarian hormones would increase inflammation, more so than testosterone making it better," says senior author Dawn Newcomb, of the Vanderbilt University Medical Centre. "I was surprised to see that testosterone was more important in reducing inflammation."
Previous studies, including one also led by Newcomb, have found that, before puberty, boys are about 1.5 times more likely than girls to experience asthma, but that the trend reverses after puberty. The pattern continues until women reach menopause, and then the asthma rates in women begin to fall.
Increased asthma symptoms are regulated by many different factors, such as exposure to allergens and viral infections, and the researchers suspected that sex hormones might also be involved.
Newcomb and her colleagues studied human and mouse cells to confirm the trend in gender differences they’d observed. They focused on lung cells called Group 2 innate lymphoid cells, or ILC2 cells. These cells make cytokines, proteins that cause inflammation and mucus production in the lungs, which make it harder to breathe. The researchers collected blood from people with and without asthma and found that those with asthma had more ILC2 cells than those without. Of that group, asthmatic women had more ILC2 cells than asthmatic men.
ILC2 cells are also found in the lungs of mice, but they are rare. They make up only about 10,000 of the 10 million cells in a mouse lung. Similar to the results that they found in humans, Newcomb and colleagues always found that they were getting fewer cells from male mice than female ones. They used the mouse cells to experiment with the effects of hormones on ILC2 cells.
When the researchers added ovarian hormones such as oestrogen and progesterone to the cells, they did not see much of a change or increase in the ability to make cytokines. However, when they added testosterone, they saw that the hormone prevented the cells from expanding and reduced cytokine production.
This study focused on testosterone, but Newcomb hopes to expand further studies to explore the effects of other sex hormones on asthma.
"Sex hormones are not the only mechanism but, rather, one of many mechanisms that could be regulating airway inflammation," she says. "This is not the only important mechanism in asthma."