Lack of a nitric-oxide response during the course ofLeishmania infantuminfection in the golden hamster (Mesocricetus auratus), with or without treatment with liposomal amphotericin B

Abstract

Liver and spleen volumes and serum concentrations of nitrate (the end-product of NO in vivo), albumin, γ-globulin, protein, creatine and urea were measured during the course of progressive infections with Leishmania infantum MON-1 (MHOM/PR/93/CRE29) in 10 Syrian golden hamsters. Each hamster was infected by intraperitoneal injection with 4 × 107 promastigotes. Five of the infected animals were treated, with 6 mg liposomal amphotericin B (L-AmB)/kg given by intracardiac injection, on day 107 post-infection (p.i.). Compared with those in the uninfected hamsters used as controls, the liver volumes in the infected animals became significantly enlarged by day 40 p.i. (38% larger than the controls; P< 0.001) whereas significant enlargement of the spleen was first detected on day 72. Each infected animal had detectable serum levels of antileishmanial antibodies on day 72. There were significant elevations in γ-globulin concentration as early as day 40 (P < 0.05) but significant falls in albumin concentrations were only detected from day 107 (P< 0.001). Nitrate, creatinine and urea concentrations remained unchanged during the course of infection, even after L-AmB treatment. Serum nitrate levels were not enhanced by L. infantum infection nor by the L-AmB treatment which induced a 98.2% decrease in parasite burden. The lack of NO production in visceral leishmaniasis, with or without L-AmB treatment, points to the unresponsiveness of inducible nitric oxide synthase in this rodent model.