Involvement of nitric oxide in protecting mechanism during experimental cryptococcosis

In the present study we investigated the role of nitric oxide (NO) in the effector mechanisms of host defense against Cryptococcus neoformans in vivo. Our results showed an increase of NO produced by the peritoneal macrophages from 14-days infected rats compared with normal rats. These cells were capable of killing C. neoformans to a greater extent than macrophages from noninfected rats (80% vs 20%, respectively). The killing of C. neoformans by infected cells was efficiently inhibited (80% to 35%, P < 0.001) by adding aminoguanidine (AG) to the cultures. We observed that in vivo administration of AG to the infected animals efficiently inhibited the metabolism producing NO and failed to affect that of normal animals. When the NO synthase (NOS) was inhibited in vivo in the infected animals, a marked increase of the fungi charge in the organs was observed with respect to the normal animals treated with AG. We also observed that the course of the infection is drastically modified after the inhibition of NO production because all the animals infected and treated with AG died from cryptococcosis before 20 days postinfection (p.i.). These results indicate that NO is a crucial molecule in the effector mechanisms in this infection model.