Involvement of nitric oxide in protecting mechanism during experimental cryptococcosis

In the present study we investigated the role of nitric oxide (NO) in the e ffector mechanisms of host defense against Cryptococcus neoformans in vivo. Our results showed an increase of NO produced by the peritoneal macrophage s from 14-days infected rats compared with normal rats. These cells were ca pable of billing C. neoformans to a greater extent than macrophages from no ninfected 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 administratio n of AG to the infected animals efficiently inhibited the metabolism produc ing NO and failed to affect that of normal animals. When the NO synthase (N OS) 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 dras tically modified after the inhibition of NO production because all the anim als infected and treated with AG died from cryptococcosis before 20 days po stinfection (p.i.). These results indicate that NO is a crucial molecule in the effector mechanisms in this infection model, (C) 1999 Academic Press.