NOVEL ANTIPNEUMOCYSTIS CARINII EFFECTS OF THE IMMUNOSUPPRESSANT MYCOPHENOLATE MOFETIL IN CONTRAST TO PROVOCATIVE EFFECTS OF TACROLIMUS, SIROLIMUS, AND DEXAMETHASONE

The effects of three new immunosuppressive drugs used for organ transp lantation, mycophenolate mofetil, tacrolimus, and sirolimus, were comp ared with those of dexamethasone in provocation of Pneumocystis carini i pneumonitis in virus-free Sprague-Dawley rats. Rats injected daily w ith tacrolimus showed a dose-related response to the point of severe P , carinii pneumonitis 4 weeks after initiation of drug administration identical to those animals treated with high-dose dexamethasone. Thirt y percent of rats treated with sirolimus had mild P. carinii infection . Surprisingly, mycophenolate mofetil had an anti-P. carinii effect. N one of the animals had discernible P. carinii infection when treated w ith mycophenolate mofetil alone or combined with dexamethasone. Mycoph enolate mofetil is unique because of its dual activity as a potent imm unosuppressant as well as an antimicrobial with action against P. cari nii.