Recovery from Pneumocystis carinii pneumonia in dexamethasone-treated Wistar rats

Abstract

Our aim was to study histopathological changes in lung tissue at the light microscopic and ultrastructural level during recovery from immunosuppression and Pneumocystis carinii pneumonia. Male Wistar rats were immunosuppressed by per oral dexamethasone for 12 weeks to induce P. carinii pneumonia, after which dexamethasone was stopped. Recovery was monitored 1, 2 and 4 weeks after cessation of the immunosuppression. In immunosuppressed animals, CD4+ and CD8+ lymphocytes were both decreased in situ. CD8+ lymphocytes increased above control level at week one. Like CD8+ cells, the ED1+ macrophages increased rapidly in situ. This was accompanied by a progressively increasing migration (more transient for lymphocytes) of macrophages into bronchoalveolar fluid, associated with morphological signs of activation and phagocytosis and proliferation of type II pneumocytes. Bronchoalveolar lavage (BAL) fluid tumour necrosis factor-α (TNF-α) increased from subnormal levels to a 4 week peak, with an inverse correlation between TNF-α and cyst count (r=-0.626). Our observations suggest a sequence of changes characterized by an increase in CD4+ cells, accompanied by a more rapid and prolonged recruitment/activation of CD8+ cells, macrophages and type II pneumocytes.