Effect of CD40 ligand and other immunomodulators on Pneumocystis carinii infection in rat model

The corticosteroid-treated animal is well established as an experimental mo del for the study of Pneumocystis carinii pneumonitis (PCP). Latent or acqu ired infection with P. carinii in the murine lung progresses to fatal pneum onitis when the host is profoundly immunocompromized. In this study the eff ects of five immunomodulators; recombinant CD40 ligand (CD40L), bryostatin 1, recombinant FLT3 ligand (FLT3L), recombinant granulocyte colony-stimulat ing factor (G-CSF) and recombinant interleukin-15 (IL-15) were investigated against PCP in a dexamethasone immunosuppressed Sprague-Dawley rat model. The majority of rats (70%) treated with CD40L at the onset of dexamethasone immunosuppression were protected against PCP. When CD40L was given after 1 0 days of immunosuppression, only 40% of the rats resolved the infection. H owever, 95% of the control animals developed PCP. Immunosuppressed rats tre ated with bryostatin 1, an immune activator had a partial (50%) protection against P. carinii infection. In contrast, daily administration of FLT3L, I L-15 or G-CSF provided no protection against P. carinii infection. (C) 2000 Academic Press.