Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis
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 intraven...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/2789859 |
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| author | Fábio Peixoto Maurício T. Nascimento Rúbia Costa Juliana Silva Gaby Renard Luiz Henrique Guimarães Gerson Penna Manoel Barral-Netto Lucas P. Carvalho Paulo R. L. Machado Edgar M. Carvalho |
| author_facet | Fábio Peixoto Maurício T. Nascimento Rúbia Costa Juliana Silva Gaby Renard Luiz Henrique Guimarães Gerson Penna Manoel Barral-Netto Lucas P. Carvalho Paulo R. L. Machado Edgar M. Carvalho |
| author_sort | Fábio Peixoto |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-1feab120833a4b5daa91f61f171185da |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-1feab120833a4b5daa91f61f171185da2025-02-03T01:01:55ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/27898592789859Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous LeishmaniasisFábio Peixoto0Maurício T. Nascimento1Rúbia Costa2Juliana Silva3Gaby Renard4Luiz Henrique Guimarães5Gerson Penna6Manoel Barral-Netto7Lucas P. Carvalho8Paulo R. L. Machado9Edgar M. Carvalho10Instituto Gonçalo Moniz, FIOCRUZ, R. Waldemar Falcão, 121, Candeal, 40296-710 Salvador, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, R. Waldemar Falcão, 121, Candeal, 40296-710 Salvador, BA, BrazilServiço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, R. Dr. Augusto Viana, s/n, Canela, 40301-155 Salvador, BA, BrazilServiço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, R. Dr. Augusto Viana, s/n, Canela, 40301-155 Salvador, BA, BrazilQuatro G Pesquisa & Desenvolvimento Ltda, Av. Ipiranga 6681, Prédio 92A, Porto Alegre 90619-900, BrazilUniversidade Federal do Sul da Bahia, Praça Joana Angélica, 58, São Jose, Teixeira de Freitas, 45988 BA, BrazilUniversidade de Brasília (UnB), Núcleo de Medicina Tropical, Brasília, 70910-900 DF, BrazilInstituto Gonçalo Moniz, FIOCRUZ, R. Waldemar Falcão, 121, Candeal, 40296-710 Salvador, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, R. Waldemar Falcão, 121, Candeal, 40296-710 Salvador, BA, BrazilServiço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, R. Dr. Augusto Viana, s/n, Canela, 40301-155 Salvador, BA, BrazilInstituto Gonçalo Moniz, FIOCRUZ, R. Waldemar Falcão, 121, Candeal, 40296-710 Salvador, BA, BrazilCutaneous 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.http://dx.doi.org/10.1155/2020/2789859 |
| spellingShingle | Fábio Peixoto Maurício T. Nascimento Rúbia Costa Juliana Silva Gaby Renard Luiz Henrique Guimarães Gerson Penna Manoel Barral-Netto Lucas P. Carvalho Paulo R. L. Machado Edgar M. Carvalho 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 |
| title | Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis |
| title_full | Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis |
| title_fullStr | Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis |
| title_full_unstemmed | Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis |
| title_short | Evaluation of the Ability of Miltefosine Associated with Topical GM-CSF in Modulating the Immune Response of Patients with Cutaneous Leishmaniasis |
| title_sort | evaluation of the ability of miltefosine associated with topical gm csf in modulating the immune response of patients with cutaneous leishmaniasis |
| url | http://dx.doi.org/10.1155/2020/2789859 |
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