Testosterone influences inflammation, may play vital role in asthma

Fluctuation in hormones levels impact inflammation of lungs in allergic asthma revealed a study published in the journal of immunology.This may open the door to sex- and age-specific treatments for asthma in future.

The researchers at John Hopkins University School of Medicine, conducted the study aimed to test a hypothesis born from a previous study that showed estrogen was an activator of immune cells that caused lung inflammation.

Asthma is a lung disease that inflames and narrows the airways. Certain elements can cause the inflamed airways to overreact resulting in an asthma attack. Asthma is a common disease that affects 300 million people worldwide. The beginning of asthma symptom is associated with an abnormal Th2 inflammatory immune response that causes increased mucus production leading to airways construction. This causes infiltration of immune cells in the lungs, alveolar macrophages are one of them which is also plentiful in the lungs. Those inflammatory molecules recruit eosinophils, which increase airway responsiveness and mucus production.

Previous studies have demonstrated that asthma is more common in males than females before puberty and more in women than men post-puberty. Sex differences in asthma suggest that sex hormones modify lung inflammation and macrophage polarization. Asthmatic women have more M2 macrophages than asthmatic men and androgens have been used as an experimental asthma treatment.

The study conducted by Mireya Becerra-Díaz et.al demonstrated that androgen (dihydrotestosterone) reconstitution of castrated mice reduces lung inflammation in a mouse model of allergic lung inflammation, it enhances M2 polarization of AM. This indicates a cell-specific role for androgens. The study also revealed that Dihydrotestosterone also enhanced IL-4–stimulated M2 macrophage polarization in vitro.

The researchers have used mouse lacking androgen receptors (AR) in monocytes/macrophages (AR^floxLysMCre) in which they found that male mouse exhibited less eosinophil recruitment and lung inflammation due to impaired M2 polarization. However, this was not seen in female mice. The researchers observed a significant reduction in eosinophil recruiting chemokines and Interleukin IL-5 in AR-deficient AM.

The scientists concluded that these data provide an unexpected and very crucial role of androgen/AR in promoting M2 macrophage polarization which has not been explored earlier. The authors feel that their finding will give an insight into the pathology of asthma and how it is influenced by M2 macrophages and androgens. Also, their findings are important for understanding pathology in diseases promoted by M2 macrophages and androgens, such as eosinophilic esophagitis, and prostate cancer, and for designing new approaches to treatment.