Killing of Leishmania donovani amastigotes by poly ICLC in hamsters.
In vitro as well as in vivo studies suggest that cytokine-induced synthesis of nitric oxide (NO) from L-arginine is a major effector mechanism against intracellular pathogens. In this study, we demonstrate that golden hamsters infected with Leishmania donovani amastigotes upon treatment with polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly ICLC), a potent interferon inducer and immune enhancer, in combination with L-arginine, develop the capacity to eliminate intracellular pathogens. This antileishmanial activity of poly ICLC was suppressed by N w nitro-L-arginine (N w NLA), an inhibitor of inducible NO synthase. Furthermore, prolonged treatment of infected animals with L-arginine alone for 5 days more after 5 day treatment with poly ICLC plus L-arginine increased the antileishmanial activity compared with 5 day treatment with poly ICLC plus L-arginine, suggesting that inducible NO synthase, once activated, produces NO for 5 days more. Our results suggest that an L-arginine-dependent, NO-mediated mechanism is probably responsible for the antileishmanial action of poly ICLC.
Bhakuni
V
V
Department of Pathology, Uniformed Services, University for the Health Sciences, Bethesda, MD 20814-4799, USA.
Singha
U K
UK
Dutta
G P
GP
Levy
H B
HB
Maheshwari
R K
RK
D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004790:Enzyme Induction; D007369:Interferon Inducers / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D008647:Mesocricetus; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D019335:Nitroarginine / Q000627:therapeutic use; D011070:Poly I-C / Q000494:pharmacology / Q000627:therapeutic use*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D007369:Interferon Inducers; D019335:Nitroarginine; D011107:Polylysine; D009569:Nitric Oxide; C019531:poly ICLC; D001120:Arginine; D019001:Nitric Oxide Synthase; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C