ANTICRYPTOCOCCAL ACTIVITY BY ALVEOLAR MACROPHAGES FROM RATS TREATED WITH CORTISONE-ACETATE DURING DIFFERENT PERIODS OF TIME

The effect of cortisone acetate (CA) treatment on the anticryptococcal activity by rat alveolar macrophages (AM) was investigated. The anima ls received a weekly dose of 5 mg CA during 1, 2, 3 or 4 weeks. Follow ing the final dose the AM were collected by lung lavage and challenged with Cryptococcus neoformans. Parallel experiments with silica partic les of a similar size were performed. The phagocytic function was asse ssed using a fluorescence method that distinguishes between attached a nd ingested particles. The oxidative metabolism was studied by the nit roblue tetrazolium (NBT) reduction test. The accumulated attachment (a measure of the attachment process) of cryptococci and silica particle s per AM was significantly depressed after the third and fourth week o f CA treatment. The ingested fraction (a measure of the ingestion proc ess) of cryptococci but not of silica particles showed a small but sig nificant decrease after the fourth week. The NET reduction of the unst imulated AM and those stimulated with either the cryptococci or silica particles for 24 h was significantly reduced after the fourth week of treatment. In conclusion, these results demonstrate that high dose CA treatment primarily affects the attachment of the cryptococci to the AM and to a lesser extent also the ingestion process. In addition, it decreases the NET reduction by AM in response to the yeast. The impair ment of the AM anticryptococcal activity by high doses of CA constitut es a risk of dissemination of C. neoformans from the lungs.