Human placental extract offers protection against experimental visceral leishmaniasis: a pilot study for a phase-I clinical trial.
An aqueous extract of human placenta (HPE) was found to offer protection against established experimental visceral leishmaniasis in BALB/c mice and hamsters, whether the Leishmania donovani strain involved was one that was sensitive or resistant to pentavalent antimony. Intraperitoneal administration of the extract, into mice or hamsters that had been infected 2 months previously, led to antileishmanial T-cell proliferation among splenic mononuclear cells, the generation of host-protective cytokines (interferon-gamma, tumour necrosis factor and interleukin-12) and the upregulation of the expression of inducible nitric oxide synthase (and subsequent NO generation) in splenocytes. Furthermore, splenic macrophages from the HPE-treated mice showed increased generation of reactive oxygen species and enhanced surface expression of antigens of major histocompatibility complex class II (MHCII), and the extract restored the otherwise-defective antigen-presenting ability of the macrophages. Thus, in mice and hamsters infected with L. donovani, HPE therapy can stimulate both arms of the host's immune system and favour the complete resolution of the leishmanial infection. Among five human cases of visceral leishmaniasis, 30 daily intramuscular injections of HPE, at doses much lower than those used in the experimental infections, also gave very promising results. Based on the results of this pilot study, a further evaluation of the efficacy of HPE therapy, which may offer a cost-effective way of improving the treatment of antimony-resistant cases of visceral leishmaniasis, is being undertaken.
Chakraborty
D
D
Department of Immunology, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.
Basu
J M
JM
Sen
P
P
Sundar
S
S
Roy
S
S
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D000913:Antibodies, Protozoan / Q000187:drug effects* / Q000276:immunology; D003411:Arvicolinae; D002648:Child; D017321:Clinical Trials, Phase I as Topic; D006224:Cricetinae; D005260:Female; D006801:Humans; D007893:Leishmania donovani / Q000469:parasitology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010865:Pilot Projects; D010924:Placental Extracts / Q000276:immunology / Q000627:therapeutic use*; D013154:Spleen / Q000187:drug effects* / Q000276:immunology
D000913:Antibodies, Protozoan; D010924:Placental Extracts