NITRIC-OXIDE INVOLVEMENT IN EXPERIMENTAL TRYPANOSOMA-CRUZI INFECTION IN CALOMYS CALLOSUS AND SWISS MICE

Nitric oxide (NO) production by peritoneal macrophages was evaluated i n Calomys callosus and Swiss mice during the course of infection with two strains of Trypanosoma cruzi. In C. callosus, no WO production was detected throughout the period of observation in animals infected wit h either parasite strain, except for a very low amount measured on day 40 in animals infected with strain M226 and on the 28th day in animal s infected with strain F after in vitro stimulation with interferon ga mma (IFN-gamma). Macrophages of Swiss mice produced large amounts of N O, the highest values being observed on the 40th day in mice infected with the F strain. Induced nitrogen oxide synthase (iNOS) was not dete cted in macrophages of infected C. callosus but was detected in mice. The i.p. inoculation of thioglycolate, bacille Calmette-Guerin (BCG) a nd periodate, nonspecific macrophage activators, did not induce NO pro duction in C. callosus, but high levels were observed in Swiss mice af ter secondary in vitro IFN-gamma plus lipopolysaccharide (LPS) stimula tion. However, H2O2 release was induced in macrophages stimulated with phorbol myristate acetate (PMA) in both experimental models. Serum NO x(NO2 + NO3) levels were low in C. callosus infected with strain M226, which was originally isolated from this animal species. Strain-F-infe cted animals had higher serum NOx levels in the initial period of infe ction. which dropped to noninfected control values on the 40th day. In Swiss mice, both strains induced the production of higher levels of N Ox throughout the period of observation, with the increase being more pronounced in mice infected with the F strain. Daily treatment of F-st rain-infected C. callosus with the arginine analogue L-nitro-arginine drastically reduced NOx levels, with no influence on parasitemia or mo rtality being observed. The results obtained suggest that C. callosus shows a distinct behavior with regard to resistance to T. cruzi infect ion.