IMMUNODEFICIENT AND IMMUNOSUPPRESSED MICE AS MODELS TO TEST ANTIPNEUMOCYSTIS CARINII DRUGS

Congenitally immunodeficient and immunosuppressed normal mice with nat urally acquired Pneumocystis carinii infection were compared as models for testing anti-P. carinii drugs. Among the immunodeficient mice, mi ce,vith severe combined immunodeficiency disease (scid), which lack B and T cells, had higher levels of P. carinii pneumonia than did mu MT mice, which lack B cells, Normal mice administered dexamethasone in th e drinking water had more extensive pneumocystosis than mice administe red parenteral methylprednisolone or hybridoma cells making a monoclon al antibody to CD4 cells, The standard anti-P. carinii drugs trimethop rim (TMP)-sulfamethoxazole (SMX), pentamidine, and atovaquone, which w ork well in rats and humans, worked well in the mice, Clindamycin and primaquine were effective in the scid and mu MT mice but not in the im munosuppressed normal mice. High doses of epiroprim, an analog of TMP, appeared to enhance the activities of low doses of SMX and dapsone, w hile high doses of TMP did not; however, further studies are needed be fore definitive conclusions about the actions of these drugs can be dr awn. Taken together, the data obtained in this study support the growi ng body of literature suggesting that the mouse is a valid alternative to the rat as a model for testing anti-P. carinii drugs. Additional d ifferences involving the activities of individual drugs in these model s will Probably emerge as more experience is gained.