The Effect of Adrenalectomy on Bleomycin-Induced Pulmonary Fibrosis in Mice

Abstract

AbstractProgressive lung fibrosis is often fatal and has limited treatment options. Though the mechanisms are poorly understood, fibrosis is increasingly linked with catecholamines such as adrenaline (AD) and noradrenaline (NA), and hormones such as aldosterone (ALD). The essential functions of adrenal glands include the production of catecholamines and numerous hormones, but the contribution of adrenal glands to lung fibrosis remains less well studied. Here, we characterized the impact of surgical adrenal ablation in the bleomycin model of lung fibrosis. Wild type mice underwent surgical adrenalectomy or sham surgery followed by bleomycin administration. We found that the bleomycin induced collagen over deposition in the lung was not affected by adrenalectomy. However, histologic indices of lung remodeling were ameliorated by adrenalectomy. These findings were accompanied by a decrease in bronchoalveolar lavage (BAL) cell count along with concomitant reductions in alpha smooth muscle actin (⍺SMA) and fibronectin. Surgical adrenalectomy completely abrogated AD detection in all compartments, but only reduced NA in the BAL of uninjured mice. Systemic ALD levels were reduced after adrenalectomy. Taken together, these results support the presence of pulmonary-adrenal axis in lung fibrosis and suggest that adrenalectomy is protective in this disease. Further investigation will be needed to better understand this observation and aid in the development of novel therapeutic strategies.