Improvement in clinical signs and cellular immunity of dogs with visceral leishmaniasis using the immunomodulator P-MAPA


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 (2.0mg/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. © 2013 Elsevier B.V.



CD4+ T, CD8+ T, Leishmania, P-MAPA, T lymphocytes, 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide, antileishmanial agent, gamma interferon, interleukin 10, interleukin 2, Leishmania antibody, phytohemagglutinin, placebo, protein aggregate magnesium ammonium phospholinoleate palmitoleate anhydride, protozoal antigen, protozoal protein, protozoon antibody, unclassified drug, antibody, antigen, blood, canid, drug, immunity, leishmaniasis, parasite, symptom, animal tissue, antibody detection, blood sampling, CD4+ T lymphocyte, CD8+ T lymphocyte, cell culture, cell stimulation, cellular immunity, clinical feature, controlled study, cytokine production, dog disease, enzyme linked immunosorbent assay, flow cytometry, immunocompetence, immunomodulation, immunostimulation, immunotherapy, in vitro study, mononuclear cell, nonhuman, parasite load, promastigote, real time polymerase chain reaction, remission, skin biopsy, symptomatology, T lymphocyte subpopulation, visceral leishmaniasis, Canis familiaris

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Acta Tropica, v. 127, n. 3, p. 174-180, 2013.