Article
Evaluation of the ability of Miltefosine associated with topical GM-CSF in modulating the immune response of patients with cutaneous Leishmaniasis
Registro en:
PEIXOTO, Fábio et al. Evaluation of the ability of Miltefosine associated with topical GM-CSF in modulating the immune response of patients with cutaneous Leishmaniasis. Journal of Immunology Research, [s.l], v. 2020, n. 2789859, p. 1-9, Aug. 2020.
2314-7156
10.1155/2020/2789859
Autor
Peixoto, Fábio de Carvalho
Nascimento, Maurício
Costa, Rúbia
Silva, Juliana
Renard, Gaby
Guimarães, Luiz Henrique
Penna, Gerson Oliveira
Barral-Netto, Manoel
Carvalho, Lucas P.
Machado, Paulo Roberto Lima
Carvalho, Edgar M.
Resumen
Gerson Oliveira Penna - Fundação Oswaldo Cruz. Fiocruz Brasília. Brasília, DF, Brasil. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento do vinculo com a unidade da Fiocruz Brasília. Ministério da Saúde e pelo Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Cutaneous leishmaniasis (CL) due to L. braziliensis is associated with an exaggerated inflammatory response and tissue damage.
Miltefosine is more effective than pentavalent antimony (Sbv
) in the treatment of CL, and here, we evaluate the ability of Sbv
,
miltefosine, and GM-CSF administered intravenously, orally, or topically, respectively, to modify the immune response. Patients
were treated with miltefosine plus GM-CSF, miltefosine plus placebo, or Sbv
. Mononuclear cells were stimulated with soluble
Leishmania antigen (SLA) on day 0 and day 15 of therapy, and cytokine levels were determined in supernatants by ELISA. The
lymphocyte proliferation and oxidative burst were evaluated by flow cytometry, and the degree of infection and Leishmania
killing by optical microscopy. Proliferation of CD4+ T cells were enhanced in patients using miltefosine and in CD8+ T cells
when GM-CSF was associated. Enhancement in the oxidative burst occurred in the miltefosine plus GM-CSF group on day 15
of therapy. Moreover, the number of L. braziliensis in infected monocytes on day 15 as well as the percentage of infected cells
was lower after 48- and 72-hour culture in cells from patients treated with miltefosine plus GM-CSF. In addition to the ability of
miltefosine to kill Leishmania, the changes in the immune response caused by miltefosine and GM-CSF may increase the cure
rate of CL patients using these drugs.