Treatment of murine cryptococcosis with cyclosporin-A in normal and athymic mice

Abstract

We previously demonstrated that prophylactic Cyclosporin-A (Cs-A) treatment of mice enhanced survival after inoculation of Cryptococcus neoformans by both the intratracheal (IT) and intravenous (IV) routes. In the present studies, we determined whether an established infection due to C. neoformans could be treated with Cs-A. Mice inoculated IT develop a prominent pulmonary infection with late dissemination to distant organs. The survival of mice infected by the pulmonary route that received Cs-A subcutaneously was prolonged in both immunologically intact and congenitally T-cell-deficient mice (athymic nude mice). In normal mice that received Cs-A, growth of C. neoformans was arrested in the lung, spleen, kidney, and liver, and the rapid rate of accumulation of organisms in the brain was slowed as compared to that of control mice. In nude mice, the organisms continued to increase in all organs although at a considerably slower rate than in untreated control nude mice. Mice given C. neoformans IV developed infection in the brain at the time of inoculation. When an inoculum was deposited in the brains of normal mice by giving the organism IV and Cs-A treatment initiated 3 days later, mice receiving Cs-A did not demonstrate a reduced number of C. neoformans in the brain as compared to untreated control mice. Thus, Cs-A was effective for treatment of extraneural cryptococcal infection in normal mice, but it was unable to reduce cryptococcal replication in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)