Aluminum Inhalation Reduces Silicosis in a Sheep Model

Abstract
In recent studies, we documented that the biologic activity of quartz can be substantialy reduced by surface chemistry modification with aluminum lactate treatment of the particles. In the present study, we evaluated the efficacy of aluminum lactate inhalation to reduce the biologic activity of experimental silicosis in the sheep tracheal lobe model. Four groups of 10 sheep were exposed once to either 100 ml phosphate-buffered saline (PBS) followed by aerosol inhalation of 10 ml PBS at monthly intervals (PBS-PBS group), to 100 ml followed by inhalation of 100 mg aluminum lactate in 10 ml PBS (Si-Al group). Bronchoalveolar lavage (BAL) was repeated at monthly intervals for 6 months from before exposure (Month 0), and all sheep were autopsied at Month 6 6. All aerosol inhalations were carried out 24 h after BAL starting at Month 1 and monthly thereafter. In the PBS-PBS group and PBS-Al group, all BAL analyses remained at control levels and lung histology remained normal. In the Si-PBS group, BAL analyses documented significant sustained 3- to 10-fold increases in macrophages, lymphocytes, neutrophils, immunoglobulins, lactate dehydrogenase, glycosaminoglycans, lecithin, and phosphatidylglycerol, immunoglobulins, lactate dehydrogenase, glycosaminoglycans, lecithin, and phosphatidylglycerol, with histopathologic changes of nodular silicosis (pathologic score, 2.9 .+-. 0.9) and mean retention of quartz at 2.83 .+-. 0.98 .mu.g/mg lung tissue. In the Si-Al group, all BAL analyses returned to control levels within 2 months after Al inhalation, the histopathologic process was significantly reduced (score = 0.9 .+-. 0.2, p < 0.05), and quartz retention was reduced significantly at 1.01 .+-. 0.74 .mu.g/mg lung tissue (p < 0.05). These data in the sheep tracheal lobe model of silicosis document that aluminum lactate inhalation 1 month after exposure significantly suppresses the silica-induced alveolitis, reduces the pathologic process, and decreases the retention of quartz in the lung tissue.