Growth characteristics and pathogenesis of experimental Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia was produced in two groups of rats by the administration of corticosteroids, a low-protein (8%) diet, and tetracycline in the drinking water. A third group not on corticosteroids or a low-protein diet served as controls. Members of the first group were sacrificed weekly for 8 weeks, and lungs were examined. A highly significant correlation was found between the histopathological assessment of the intensity of P. carinii infection and the number of cysts counted in enzyme-digested lungs. P. carinii progressively filled alveoli, and cyst counts increased from less than or equal to 10(4) to 10(9) cysts/g of lung at peak intensity of infection at 7 to 8 weeks. The second group of rats was placed on a regular diet and tapering doses of corticosteroids after week 4, and they were sacrificed at varying intervals for up to 21 weeks. P. carinii was not cleared from the lungs until after week 13 (more than 6 weeks after discontinuation of all steroids). Histologically, there was an increased prominence of alveolar macrophages and the progressive development of interstitial mononuclear cell infiltrate and fibrosis. Thus, P. carinii grows grows slowly in vivo and interacts with specific host cells. The resulting changes may be important in the pathogenesis of the infection and in the clearance of the organism from the lung after immunocompetence has been restored.