Experimental corticosteroid induction of Pneumocystis carinii pneumonia in piglets

Animal models of Pneumocystis carinii (Pc) pneumonia (PCP) play a central role in research on the Pc microorganism itself and the disease, especially the pathogenesis and the host defence. The classic rat model with corticosteroid-induced reactivation of a latent infection has been most widely used. In our search for alternative non-rodent models, six 31/2-week-old piglets were injected intramuscularly with methylprednisolone acetate, at 18 mg/kg body weight, once a week for 6 weeks. Six littermate piglets constituted the control group. The principals showed a markedly lower growth rate than the controls. Furthermore, they developed "moon face" and "pot belly", snoring sounds while eating, and pronounced respiratory distress during handling. Significant changes in haematological parameters, including lymphopenia, were observed in the principal group. The Pc antibody titres of the controls increased to high levels, whereas the principals were all low-titred or seronegative for Pc at the last blood sampling. At necropsy, the mean body weight of the principals was about half that of the controls. In addition, they had an extreme reduction of the thymus together with dark red consolidations of the frontal lung lobes and/or atelectatic looking diaphragmatic lobes. Histopathologically, there was a focal interstitial pneumonia. Alveolar walls and interstitia had mononuclear cell infiltrations and the alveolar lumina were occluded by foamy acidophilic honeycomb material with a varying number of Pc cysts. The reduced body weight, the thymus involution, and the lymphopenia, together with the reduced levels of specific Pc antibodies and the histomorphology of the PCP, were consistent parameters of the principal group and comparable to the findings of the classic rat model. Thus, the present study is the first to describe that prolonged administration of high doses of methylprednisolone acetate can induce PCP in piglets.