We have previously shown that neuroendocrine activation leading to increased circulating stress hormones was necessary for mediating ozone-induced lung injury and inflammation since adrenalectomy rats were protected from these ozone effects. Because adrenalectomy is invasive and also eliminates circulating mineralocorticoids along with stress hormones, one cannot rule out their contribution in diminution of ozone-induced lung effects. The goal of this study was to evaluate if agonists of stress hormone receptors β2 adrenergic receptors and glucocorticoid receptors were able to restore ozone-induced lung injury, inflammation and innate immune cell trafficking in adrenalectomy rats, and exacerbate these effects in control rats with sham surgery. Here, we reconfirmed that the pulmonary and systemic effects of ozone inhalation, characterized by vascular leakage, neutrophilic inflammation, cytokine release in the lungs and peripheral vascular lymphopenia, were significantly diminished by adrenlectomy. The treatment with a combination of β2 adrenergic receptor and glucocorticoid receptor agonists (Clenbuterol and dexamethasone) was able to restore these ozone effects in AD rats, and further exacerbate ozone-induced lung protein leakage, inflammation and lymphopenia in sham surgery rats. It was also noted that clenbuterol plus dexamethasone itself caused injury and cytokine increases in the lung. Although a variety of β2 adrenergic receptor and glucocorticoid agonists have been widely used for the treatment of chronic lung diseases, β2 adrenergic receptor agonists have been shown to exacerbate lung inflammation in asthmatics and epidemiological studies have indicated exacerbation of lung inflammation in asthmatics during increased air pollution episodes. Even though high concentrations of agonists were used, our study provides a potential causal mechanistic link between activation of stress hormone receptors in mediation of air pollution health effects, and how these effects might be exacerbated in those receiving asthma therapy.

This dataset is associated with the following publication: Henriquez, A., S. Snow, M. Schladweiler, C. Miller, J. Dye, A. Ledbetter, J. Richards, M. Hargrove, W. Williams, and U. Kodavanti. Beta-2 adrenergic and glucocorticoid receptor agonists modulate ozone-induced pulmonary protein leakage and inflammation in healthy and adrenalectomized rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 166(2): 288-305, (2018).