Nitric oxide involvement in experimental Trypanosoma cruzi infection in Calomys callosus and Swiss mice

Nitric oxide (NO) production by peritoneal macrophages was evaluated in Calomys callosus and Swiss mice during the course of infection with two strains of Trypanosoma cruzi. In C. callosus, no NO production was detected throughout the period of observation in animals infected with 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 animals infected with strain F after in vitro stimulation with interferon gamma (IFN-gamma). Macrophages of Swiss mice produced large amounts of NO, the highest values being observed on the 40th day in mice infected with the F strain. Induced nitrogen oxide synthase (iNOS) was not detected in macrophages of infected C. callosus but was detected in mice. The i.p. inoculation of thioglycolate, bacille Calmette-Guérin (BCG) and periodate, nonspecific macrophage activators, did not induce NO production in C. callosus, but high levels were observed in Swiss mice after secondary in vitro IFN-gamma plus lipopolysaccharide (LPS) stimulation. However, H2O2 release was induced in macrophages stimulated with phorbol myristate acetate (PMA) in both experimental models. Serum NOx(NO2 + NO3) levels were low in C. callosus infected with strain M226, which was originally isolated from this animal species. Strain-F-infected animals had higher serum NOx levels in the initial period of infection, which dropped to noninfected control values on the 40th day. In Swiss mice, both strains induced the production of higher levels of NOx throughout the period of observation, with the increase being more pronounced in mice infected with the F strain. Daily treatment of F-strain-infected C. callosus with the arginine analogue L-nitro-arginine drastically reduced NOx levels, with no influence on parasitemia or mortality being observed. The results obtained suggest that C. callosus shows a distinct behavior with regard to resistance to T. cruzi infection.