A canine model of beryllium-induced granulomatous lung disease

Groups of beagle dogs were exposed by inhalation to attain either low or high initial lung burdens (ILB) of BeO calcined at 500 degrees or 1000 degrees C. Dogs were killed at 8, 32, 64, 180, and 365 days after exposure for evaluation of beryllium tissue burdens and histopathologic examination. Histologic lesions were characterized by perivascular and peribronchiolar infiltrates of lymphocytes and macrophages 8 days after exposure. These lesions progressed to distinct microgranulomas accompanied by patchy granulomatous pneumonia. Lesions were more severe in dogs exposed to 500 degrees C BeO. Additional dogs were sampled by bronchoalveolar lavage at 3, 6, 7, 11, 15, 18, and 22 months after exposure for characterization of lung cytology and lung immune responses. Lymphocyte percentages and numbers were increased in lavage samples 3 months after exposure in dogs with both the high and low ILB of 500 degrees C. Values for both parameters decreased rapidly thereafter. Dogs with either low or high ILB of 1000 degrees C-treated BeO displayed negligible to low and variable changes in both lymphocyte percentages and numbers. In vitro lymphocyte stimulation by beryllium was increased 180 and 210 days after exposure in dogs with the high ILB 500 degrees C BeO only. A marked degree of individual variation in both histologic lesions and lymphocyte responses among dogs was noted. Less soluble 1000 degrees C-treated BeO was retained in the lung longer than the more soluble 500 degrees C-treated material that was cleared almost entirely by 1 year after exposure. Because these changes are similar to those reported in humans with chronic beryllium disease, these data suggest that the beagle represents a good model to study histologic and immunologic aspects of this disease syndrome.