title: Meglumine antimonate directly increases phagocytosis, superoxide anion and TNF-alpha production, but only via TNF-alpha it indirectly increases nitric oxide production by phagocytes of healthy individuals, in vitro.
abstract: Leishmania has developed mechanisms to escape from immune defense of phagocytes by inhibiting microbicidal oxygen and nitrogen radicals. This work evaluated the influence of meglumine antimonate (Sb(V)) on the phagocyte functions involved in the defense against leishmania, through phagocytosis, reactive oxygen, nitrogen and TNF-alpha production in the absence or presence of the drug, in vitro. Meglumine antimonate increased the number of Saccharomyces cerevisiae ingested by monocyte and the percentage of these cells engaged in phagocytosis, which resulted in an increase of the monocyte phagocytic index by 158%. Meglumine antimonate also increased the number of S. cerevisiae ingested by neutrophil and the percentage of these cells engaged in phagocytosis, increasing the neutrophil phagocytic index by 219%. The median of percent reduction of NBT was significantly increased after treatment with this pentavalent antimony from 89.5% to 96.5%. Meglumine antimonate had no influence on nitric oxide production, but it significantly increased the mean+/-SEM production of tumor necrosis factor by 230%. However, monocytes incubated with TNF significantly increased NO production. This antimonial increased the phagocytic capacity of monocytes and neutrophils and enhanced superoxide anion production by phagocytes, which represent the first line of defense against the parasite. Furthermore, meglumine antimonate increased TNF, and via this cytokine, it may also indirectly increase NO production. Our data suggest that these immunomodulatory effects of meglumine antimonate may play a role in fighting leishmania and that meglumine antimonate provides the phagocytes with a mechanism that prevents leishmania from escaping immune defense.
authors.affiliation: Laboratory of Cellular Immunology, Faculty of Medicine, University of Brasilia, Brasilia, Brazil, 70.910-900. mimjunqueira@unb.br
authors.forename: Maria Imaculada
authors.initials: MI
authors.lastname: Muniz-Junqueira
authors.forename: Viviany Nicolau
authors.initials: VN
authors.lastname: de Paula-Coelho
mesh_terms: D000328:Adult; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007896:Leishmaniasis / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008536:Meglumine / Q000494:pharmacology*; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D008536:Meglumine; D000077485:Meglumine Antimoniate