Androgens augment pulmonary responses to ozone in mice

Androgens augment ozone-induced AHR and likely contribute to the augmented responses to ozone observed in male mice. AbstractOzone causes airway hyperresponsiveness, a defining feature of asthma, and is an asthma trigger. In mice, ozone ‐induced airway hyperresponsiveness is greater in males than in females, suggesting a role for sex hormones in the response to ozone. To examine the role of androgens in these sex differences, we castrated 4‐week‐old mice. Controls underwent sham surgery. At 8 weeks of age, mice were exposed to ozone (2ppm, 3 h) or room air. Twenty‐four hours later, mice were anesthetized and measurements of airway responsiveness to inhaled aerosolized methacholine were made. Mice were then euthanized and bronchoalveolar lavage was performed. Castration attenuated ozone‐induced airway hyperresponsi veness and reduced bronchoalveolar lavage cells. In intact males, flutamide, an androgen receptor inhibitor, had similar effects to castration. Bronchoalveolar lavage concentrations of several cytokines were reduced by either castration or flutamide treatment, but only IL‐1α was reduced by both c astration and flutamide. Furthermore, an anti‐IL‐1α antibody reduced bronchoalveolar lavage neutrophils in intact males, although it did not alter ozone‐induced airway hyperresponsiveness. Our data indicate that androgens augment pulmonary responses to ozone and that IL‐1α may contribute t o the effects of androgens on ozone‐induced cellular infla...
Source: Physiological Reports - Category: Physiology Authors: Tags: Original Research Source Type: research