Immune responses of Leishmania donovani infected BALB/c mice following treatment with free and vesicular sodium stibogluconate formulations.
The anti-parasitic efficacy of free and a non-ionic surfactant vesicular (NIV) sodium stibogluconate (SSG) formulation of the drug, and their effect on the immune responses of Leishmania donovani infected BALB/c mice, was compared. The SSG NIV formulation maintained a significant suppression of splenic, hepatic and bone marrow parasite burdens (P < 0.005) compared to control values throughout the study. Infected controls and drug treated animals had high levels of L. donovani specific antibodies by day 14 of the study and the titre of these antibodies increased throughout the study for infected controls and free SSG treated animals. Initially SSG NIV treated animals had significantly higher specific IgG2a levels (P < 0.01, day 16) compared with infected controls and free SSG treated mice, but by day 31 the levels of this isotype and other antibodies (IgG1, IgG3 and IgM) were significantly lower (P < 0.05) than values for the other two groups. There was no difference in the proliferative responses of spleen cells taken from infected controls and drug treated animals to both specific and non-specific stimulation at day 16 of the study. On day 31, only spleen cells taken from infected mice given SSG NIV displayed a significant proliferative response to parasite antigen preparations and Concanavalin A stimulation (P < 0.01). No IL4 was detected in supernatants from in vitro spleen cells cultures. Significant levels of IFN-gamma was induced by stimulation of cells from vesicular drug treated animals with a frozen parasite preparation compared with medium controls (P < 0.05) on day 49 but not day 16. Similar stimulation did not induce IFN gamma production in spleen cells from infected controls or free drug treated animals. Only SSG NIV treated animals gave a significant positive DTH response to an L. donovani parasite preparation (P < 0.05) given on day 31. The results of this study indicate that there was a formulation dependent qualitative difference in the post-treatment immune responses of L. donovani infected animals, with SSG NIV animals displaying immune responses expected for a cured phenotype.
Banduwardene
R
R
Department of Immunology, University of Strathclyde, Glasgow, U.K.
Mullen
A B
AB
Carter
K C
KC
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000967:Antimony Sodium Gluconate / Q000008:administration & dosage / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D013501:Surface-Active Agents / Q000008:administration & dosage
D000913:Antibodies, Protozoan; D000981:Antiprotozoal Agents; D004337:Drug Carriers; D013501:Surface-Active Agents; D015847:Interleukin-4; D007371:Interferon-gamma; D000967:Antimony Sodium Gluconate