Testosterone may act as a promoter of lung inflammation in response to the allergen ovalbumin (OVA), indicating that the sex hormone may be an additional inflammatory pathway to allergic asthma, according to recent research published in The Journal of Immunology.

While previous studies have shown a protective effect of testosterone against allergic asthma in male mouse models, these new results suggest age and gender may play a role in the effects of these sex hormones, researchers said.

Lung inflammation. Source: Getty

“We have long known that asthma is more prevalent in pre-adolescent boys than in same-age girls, and that at puberty, when specific sex hormones increase, this switches, so that more teenage and adult women suffer from asthma than teenage and adult men,” Nicola Heller, PhD, associate professor in the Department of Anesthesiology and Critical Care Medicine at Johns Hopkins University School of Medicine, stated in a press release. “This obviously suggests that sex hormones and changes in sex hormones play a role in the pathogenesis of asthma, so a better understanding of precisely how sex hormones change the immune system’s response to allergens has the potential to help us tailor asthma therapy more specifically to the sex of each patient.”

The researchers created OVA-induced allergic lung inflammation in castrated mice for the new study and then injected the mice with androgen (dihydrotestosterone) or placebo pellets. They found that androgen reduced lung inflammation but enhanced IL-4–stimulated M2 polarization of alveolar macrophages (AM), which “turned our original hypothesis on its head,” Dr. Heller said.

Heller and colleagues then used male mice lacking androgen receptor in monocytes/macrophages and discovered male mice, but not female mice, showed decreased eosinophil recruitment and lower lung inflammation, which the researchers attributed to the missing androgen receptor. When these male mice were exposed to the OVA, there was a reduction in “eosinophil-recruiting chemokines and IL-5 in AR-deficient AM,” researchers said.

“Overall, our study affirms the need for physicians to really pay attention to where in their lifespan their patients are and to think about the role of sex hormones as augmenters of disease,” Heller said in the release.

The researchers noted in their study that knowledge of androgens enhancing M2 macrophage polarization could pave the way for new therapies for diseases like asthma and prostate cancer “thought to be worsened by M2 macrophage polarization and sex hormones.”

“A deeper understanding of the mechanisms by which androgen/AR enhances M2 macrophage polarization will help us to develop effective therapies against diseases in which M2 macrophages are important mediators,” the researchers concluded.