The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice

Progressive 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 the 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 although bleomycin-induced collagen overdeposition in the lung was not affected by adrenalectomy, histologic indices of lung remodeling were ameliorated. These findings were accompanied by a decrease of lymphocytes in bronchoalveolar lavage (BAL) and macrophages in lung tissues, along with concomitant reductions in alpha-smooth muscle actin (αSMA) and fibronectin. Surgical adrenalectomy completely abrogated AD, not NA, detection in all compartments. Systemic ALD levels were reduced after adrenalectomy, whereas ALD levels in lung tissues remained unaffected. Taken together, these results support the presence of a 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.NEW & NOTEWORTHY The lung-adrenal axis plays a significant role in pulmonary fibrosis. Adrenalectomy provides protection against lung fibrotic ECM remodeling and lung inflammation by reducing the levels of lymphocytes in BAL and macrophages in lung of bleomycin-treated mice. Although compared with sham surgery, adrenalectomy raised collagen concentration in uninjured mice, there was no discernible difference in bleomycin-induced collagen accumulation. However, adrenalectomy significantly reversed the enhanced expression and colocalization of αSMA and fibronectin induced by bleomycin.