title: CpG oligodeoxynucleotide 2006 and miltefosine, a potential combination for treatment of experimental visceral leishmaniasis.
abstract: In view of the severe immunosuppression in visceral leishmaniasis (VL), a rational approach to effectively combat the parasitic scourge would be to enhance the immune status of the host. Use of CpG oligodeoxynucleotide (CpG-ODN) against leishmaniasis has previously been reported, especially as an immunomodulator and adjuvant with various immunogens. In the present study, experiments were carried out with BALB/c mice and hamsters infected with Leishmania donovani. Immunostimulating class B bacterial CpG-ODN namely, ODN-2006, was administered at various doses by the intraperitoneal (i.p.) route. The dose of CpG-ODN-2006 (1 nM/single dose) showing the most antileishmanial activity was given as free and liposomal forms with different doses of miltefosine, namely, 5 and 10 mg/kg of body weight, for 5 days in mice and hamsters, respectively. Among the various groups, mice coadministered liposomal CpG-ODN and miltefosine (5 mg/kg) showed the best inhibitory effect (97% parasite inhibition) compared with free CpG-ODN plus miltefosine and miltefosine, free CpG-ODN, and liposomal CpG-ODN given separately. Similar responses were observed in the case of hamsters, where the combination of liposomal CpG-ODN with miltefosine (10 mg/kg) gave 96% parasite inhibition. Promising antileishmanial efficacy was observed in animals treated with liposomal CpG-ODN and miltefosine.
authors.affiliation: Division of Parasitology, Central Drug Research Institute, Lucknow, India. suman_gupta@cdri.res.in
authors.forename: Suman
authors.initials: S
authors.lastname: Gupta
authors.forename: Shraddha A
authors.initials: SA
authors.lastname: Sane
authors.forename: Nishi
authors.initials: N
authors.lastname: Shakya
authors.forename: Preeti
authors.initials: P
authors.lastname: Vishwakarma
authors.forename: W
authors.initials: W
authors.lastname: Haq
mesh_terms: D000818:Animals; D006224:Cricetinae; D004338:Drug Combinations; D005260:Female; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014344:Trypanocidal Agents / Q000627:therapeutic use*
chemical_list: C408982:CPG-oligonucleotide; D004338:Drug Combinations; D009838:Oligodeoxyribonucleotides; D014344:Trypanocidal Agents; D010767:Phosphorylcholine; C039128:miltefosine