title: Miltefosine enhances phagocytosis but decreases nitric oxide production by peritoneal macrophages of C57BL/6 mice.
abstract: Miltefosine is an anticancer drug currently used to treat visceral and cutaneous leishmaniasis, also presents a broad-spectrum of fungicidal and antiamoebae activities. It acts on the metabolism of phospholipids and glycoproteins of the membrane of parasites. Our study aimed to evaluate the effects of miltefosine (0.4 to 50.0 μg/mL) on the phagocytosis and nitric oxide production by macrophages of C57BL/6 mice to clarify the immunomodulatory effects of the drug on macrophages of C57BL/6, strain mice that is biased to Th1 response. Peritoneal macrophages were in vitro treated with miltefosine and phagocytosis of sensitized or nonsensitized Saccharomyces cerevisiae was assessed. NO production was evaluated by Griess reaction. In the concentration of 1.6 μg/mL and 50.0 μg/mL, miltefosine increased phagocytosis of non-opsonized S. cerevisiae in 59.7% and 214.3%, respectively. For phagocytosis through opsonin receptors, miltefosine (50.0 μg/mL) increased the phagocytic index in 208.6% (p=0.04, paired t test). Miltefosine (50.0 μg/mL) decreased in 39.3% NO production by macrophages. However, treatment with miltefosine (50.0 μg/mL) after infection of macrophages with Leishmania amazonensis increased NO production in 73.4% (p=0.01, Wilcoxon test). Our data showed that, besides the antimicrobial effect of miltefosine, the drug showed immunomodulatory effects on macrophages of C57BL/6 mice, improving phagocytosis and decreasing NO production, but was able to increase NO production when macrophages were previously infected with L. amazonensis. These results suggest that miltefosine may favor the better evolution of infectious diseases by improving the innate immune response of macrophages.
authors.affiliation: Laboratory of Dermatomicology, Faculty of Medicine, University of Brasilia, Brasilia-DF, Brazil.
authors.forename: Charlene Barreto
authors.initials: CB
authors.lastname: Ponte
authors.forename: Erica Alessandra Rocha
authors.initials: EA
authors.lastname: Alves
authors.forename: Raimunda Nonata Ribeiro
authors.initials: RN
authors.lastname: Sampaio
authors.forename: Ada Amalia Ayala
authors.initials: AA
authors.lastname: Urdapilleta
authors.forename: Carlos dos Santos
authors.initials: Cdos S
authors.lastname: Kückelhaus
authors.forename: Maria Imaculada
authors.initials: MI
authors.lastname: Muniz-Junqueira
authors.forename: Selma Aparecida Souza
authors.initials: SA
authors.lastname: Kückelhaus
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology*; D007891:Leishmania / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000096:biosynthesis*; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000276:immunology
chemical_list: D007155:Immunologic Factors; D010767:Phosphorylcholine; D009569:Nitric Oxide; C039128:miltefosine