KILLING OF LEISHMANIA-DONOVANI AMASTIGOTES BY POLY ICLC IN HAMSTERS

In vitro as well as in vivo studies suggest that cytokine-induced synt hesis of nitric oxide (NO) from L-arginine is a major effector mechani sm against intracellular pathogens. In this study, we demonstrate that golden hamsters infected with Leishmania donovani amastigotes upon tr eatment with polyinosinic-polycytidylic acid stabilized with polylysin e and carboxymethylcellulose (poly ICLC), a potent interferon inducer and immune enhancer, in combination with L-arginine, develop the capac ity to eliminate intracellular pathogens, This antileishmanial activit y of poly ICLC was suppressed by N-w nitro-L-arginine (N-w NLA), an in hibitor of inducible NO synthase. Furthermore, prolonged treatment of infected animals with L-arginine alone for 5 days more after 5 day tre atment with poly ICLC plus L-arginine increased the antileishmanial ac tivity compared with 5 day treatment with poly ICLC plus L-arginine, s uggesting that inducible NO synthase, once activated, produces NO for 5 days more. Our results suggest that an L-arginine-dependent, NO-medi ated mechanism is probably responsible for the antileishmanial action of poly ICLC.