Experimental Pneumocystis carinii pneumonia in different strains of cortisonized mice

Abstract

Pneumocystis carinii pneumonia was produced in eight different strains of mice by the administration of corticosteroids, low (8%)-protein diet, and tetracycline in the drinking water. Heavier degrees of P. carinii infection were most consistently found in C3H/HeN mice; intermediate levels occurred in BALB/c AnN, C57BL/6N, B1O.A(2R), AKR/J, and Swiss Webster mice; lighter degrees were found in DBA/2N and DBA/IJ mice. Histopathologically, P. carinii organisms were morphologically indistinguishable from human and rat P. carinii, and elicited a predominantly mononuclear response that was similar among the various mouse strains. The optimal cortisone acetate regimen was 1 mg injected subcutaneously twice weekly. Higher doses shortened the life span of the mice, presumably by inducing overwhelming bacterial infection. This problem occurred not only in different strains of mice, but also in the same strain of mice obtained from different breeders. Thus, cortisonized mice should be useful in the study of experimental P. carinii infection. Success of this model depends on the corticosteroid dose, as well as the strain, source, general health, and preexisting microbial flora of the mice chosen for study.

Activity of antifolates against Pneumocystis carinii dihydrofolate reductase and identification of a potent new agent.

“…Groups of 30 leucovorin-treated animals were randomized to receive a 21-d course of nothing additional, oral trimethoprim-sulfa, or oral trimetrexate-sulfa while corticosteroids were continued. Pneumocystis scores at the end of treatment (based on the percent of alveoli involved with P. carinii) (19) demonstrated that either treatment greatly diminished the quantity of organisms. Trimetrexatesulfa-treated rats had fewer organisms, with 23 of 30 animals having <1% infected alveoli, while trimethoprim-sulfa-treated rats had 16 of 30 animals, and controls only 3 of 30 animals with <1% infected alveoli (our unpublished observations).…”

Growth characteristics and pathogenesis of experimental Pneumocystis carinii pneumonia

“…Animal models of P. carinii pneumonia have traditionally been based on the reactivation of latent infection by the administration of corticosteroids. Rats and, to a lesser extent, rabbits and mice have been used for this purpose (5,24,31,35,36). Recently, exogenous P. carinii infection has been transmitted to athymic (nude) mice (26,33); however, the light intensity of infection so far achieved suggests that this animal model might be more useful in studies of epidemiology rather than of pathogenesis.…”

“…Mice. We have recently reported the development of Pneumocystis pneumonia in different strains of steroid-treated normal mice (31). The same procedures for histological examination and quantitation of P. carinii in lungs have been used for rats and mice.…”

Autopsy case of alcoholic hepatitis and cirrhosis treated with corticosteroids and affected by Pneumocystis carinii and cytomegalovirus pneumonia

“…Moreover, long-term administration of corticosteroids can produce experimental P. carinii pneumonia in animals treated or not treated with antibiotics. [13][14][15][16] In rats treated with corticosteroids, the alveolar cell-surface glycocalyx, where P. carinii attaches, decreases markedly, which suggests that corticosteroids contribute to the pathogenesis of pulmonary injury. 17 Treatment with corticosteroids would be warranted in otherwise refractory cases of alcoholic hepatitis, but careful attention should be paid to unexpected opportunistic infections and gastrointestinal bleeding.…”