title: Improvement in clinical signs and cellular immunity of dogs with visceral leishmaniasis using the immunomodulator P-MAPA.
abstract: This study investigated the immunotherapeutic potential of the protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride immuno-modulator (P-MAPA) on canine visceral leishmaniasis. Twenty mongrel dogs presenting clinical symptoms compatible with leishmaniasis and diagnosis confirmed by the detection of anti-leishmania antibodies were studied. Ten dogs received 15 doses of the immunomodulator (2.0 mg/kg) intramuscularly, and 10 received saline as a placebo. Skin and peripheral blood samples were collected following administration of the immunomodulator. The groups were followed to observe for clinical signals of remission; parasite load in the skin biopsies using real-time PCR, the cytokines IL-2, IL-10 and IFN-γ in the supernatant of peripheral blood mononuclear cells stimulated in vitro with either total promastigote antigen or phytohemagglutinin measured by capture ELISA, and changes in CD4⁺ and CD8⁺ T cell subpopulations evaluated by flow cytometry. Comparison between the groups showed that treatment with the immunomodulator promoted improvement in clinical signs and a significant reduction in parasite load in the skin. In peripheral blood mononuclear cell cultures, supernatants showed a decrease in IL-10 levels and an increase in IL-2 and IFN-γ. An increase in CD8⁺ T cells was observed in peripheral blood. In addition, the in vitro leishmanicidal action of P-MAPA was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and no leishmanicidal activity was detected. These findings suggest that P-MAPA has potential as an immunotherapeutic drug in canine visceral leishmaniasis, since it assists in reestablishing partial immunocompetence of infected dogs.
authors: Faculty of Agricultural and Veterinarian Sciences (FCAV), São Paulo State University (UNESP), Jaboticabal, SP, Brazil.
authors: Maria Emília B
authors: ME
authors: Santiago
authors: Luiz Silveira
authors: LS
authors: Neto
authors: Eduardo Costa
authors: EC
authors: Alexandre
authors: Danísio Prado
authors: DP
authors: Munari
authors: Mariana Macedo C
authors: MM
authors: Andrade
authors: Marcos Arruda
authors: MA
authors: Somenzari
authors: Paulo César
authors: PC
authors: Ciarlini
authors: V M F
authors: VM
authors: de Lima
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004283:Dog Diseases / Q000276:immunology / Q000473:pathology*; D004285:Dogs; D005260:Female; D005656:Fungal Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D018314:Leishmania infantum; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000473:pathology / Q000662:veterinary*; D008099:Liver / Q000187:drug effects; D008297:Male
chemical_list: D000981:Antiprotozoal Agents; D005656:Fungal Proteins; D007155:Immunologic Factors; D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CD4(+) T; CD8(+) T; Leishmania; P-MAPA; T lymphocytes