EXPERIMENTAL POLYMYXIN B-INDUCED INTERSTITIAL LUNG-DISEASE CHARACTERIZED BY AN ACCUMULATION OF CYTO-TOXIC EOSINOPHILS IN THE ALVEOLAR STRUCTURES

Abstract
A variety of lung disorders are associated with the accumulation of eosinophils in the alveolar structures. To help understand the role of eosinophils in these disorders, an animal model of eosinophilic lung disease was developed. Administration of an aerosol of polymyxin B to guinea pigs (3 times/wk for 4 wk) produced diffuse interstitial lung disease with alveolar wall thickening and an alveolitis characterized by marked increase in eosinophils and alveolar macrophages. Bronchoalveolar lavage confirmed the presence of significantly increased numbers of eosinophils and alveolar macrophages in polymyxin-B-treated animals compared with those in control animals. Using density gradient centrifugation, .apprx. 107 eosinophils could be purified from the lungs of a single polymyxin-B-treated animal. Importantly, eosinophils purified from the lungs from polymyxin B-treated animals exhibited significantly spontaneous cellular cytotoxicity for human fetal lung fibroblasts. In contrast, neither eosinophils from control animals nor alveolar macrophages from either group of animals were cytotoxic. Eosinophils evidently possess effector processes capable of injuring the lung parenchyma. Eosinophils may contribute to the pathogenesis of the interstitial lung disease.