Testosterone levels control the numbers of a rare subset of white blood cells that are involved in airway inflammation and asthma, a study reports. The finding helps to explain previously observed differences in asthma prevalence between adult men and women.
Sex hormones usually drive male-female differences seen in autoimmune diseases. In adults, the prevalence of asthma is twice as high in women as men, but in children, asthma is more often found in boys than girls.
The shift in prevalence usually starts at puberty, coinciding with changes in sex hormones.
Lung innate lymphoid cells (ILCs) are a subset of white blood cells that are involved in initiating inflammatory responses. A rare subset of ILCs, known as ILC2, has been shown to be involved in allergic responses and asthma, but the mechanisms that regulate ILC2 are not entirely clear.
A research group headed by Dawn Newcomb, an assistant professor at Vanderbilt University School of Medicine, investigated the possibility that women having higher numbers of ILC2 and that this might affect their risk of asthma.
The study “Testosterone Attenuates Group 2 Innate Lymphoid Cell-Mediated Airway Inflammation” was published in the journal Cell Reports.
Researchers compared ILC2 levels circulating in the blood of adult (18-45 years of age) asthmatic men and women, and in healthy controls.
No difference in ILC2 numbers were found among healthy men and women; however, women with asthma had higher numbers of ILC2 compared to men with asthma.
Using female and male adult mice, the researchers then showed that sex hormones played a role in regulating levels of ILC2. Testosterone negatively affected — lowered — ILC2 numbers. This effect was mediated by the cytokine interleukin 2 (IL-2), and was more pronounced in adult female mice compared to pre-pubescent females and males.
Testosterone also reduced the level of inflammation mediated by ILC2.
The study suggests that the level of testosterone and its effects on ILC2 explains, in part, differences seen in asthma prevalence observed between adult women and men, and may be useful in trials to better treat this and similar diseases.
“Defining the role of sex hormones on ILC2-mediated airway inflammation is imperative to effectively design future clinical trials and develop new therapeutic strategies for asthma and other ILC2-mediated diseases,” the researchers concluded.
The incidence of asthma nearly doubled worldwide between 1990 and 2015, according to a press release.