Immunochemotherapy for Leishmania donovani infection in golden hamsters: combinatorial action of poly ICLC plus L-arginine and sodium stibogluconate (Stibanate).
We demonstrate that golden hamsters infected with Leishmania donovani amastigotes develop the capacity to eliminate intracellular pathogens on treatment with low-dose standard antileishmanial sodium stibogluconate (Stibanate) in combination with polyinosinic-polycytidilic acid stabilized with polylysine and carboxymethycellulose (poly ICLC), a potent inducer of interferon (IFN) and immune enhancer, plus L-arginine. Data suggest that low doses of both Stibanate and poly ICLC plus L-arginine provide marginal inhibition against L. donovani infection in golden hamsters. When given in combination, however, a significant inhibition was achieved without toxicity, as all the animals survived up to 45 or 60 days. These results suggest that combination therapy using Stibanate and poly ICLC plus L-arginine may be very effective in reducing the dose of Stibanate and, hence, its dose-dependent toxicity in clinical situations.
Bhakuni
V
V
Division of Membrane Biology, Central Drug Research Institute, Lucknow, India.
Kulkarni
S
S
Ali
V
V
Singh
U K
UK
Levy
H B
HB
Maheshwari
R K
RK
D000818:Animals; D000967:Antimony Sodium Gluconate / Q000627:therapeutic use*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007167:Immunotherapy / Q000379:methods*; D007369:Interferon Inducers / Q000627:therapeutic use*; D007893:Leishmania donovani; D007898:Leishmaniasis, Visceral / Q000628:therapy*; D008297:Male; D008647:Mesocricetus; D011070:Poly I-C / Q000627:therapeutic use*; D011107:Polylysine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D007369:Interferon Inducers; D011107:Polylysine; C019531:poly ICLC; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C; D000967:Antimony Sodium Gluconate