Novel anti-Pneumocystis carinii effects of the immunosuppressant mycophenolate mofetil in contrast to provocative effects of tacrolimus, sirolimus, and dexamethasone.

Abstract

The effects of three new immunosuppressive drugs used for organ transplantation, mycophenolate mofetil, tacrolimus, and sirolimus, were compared with those of dexamethasone in provocation of Pneumocystis carinii pneumonitis in virus-free Sprague-Dawley rats. Rats injected daily with 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. Thirty percent of rats treated with sirolimus had mild P. carinii infection. Surprisingly, mycophenolate mofetil had an anti-P. carinii effect. None of the animals had discernible P. carinii infection when treated with mycophenolate mofetil alone or combined with dexamethasone. Mycophenolate mofetil is unique because of its dual activity as a potent immunosuppressant as well as an antimicrobial with action against P. carinii.