Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/116591 |
Resumo: | Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery. |
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Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatmentAllopurinolBone marrowCanine leishmaniosisCytokine gene expressionLymph nodeMeglumine antimoniateMiltefosinePeripheral blood mononuclear cellsCanine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery.Vector borne diseases and pathogens (VBD)Global Health and Tropical Medicine (GHTM)RUNMarcos Ferreira, Santos,Graça Maria, Alexandre-Pires,Pereira, Maria ACátia S., Marques,Gomes, JoanaJorge Jesus, Correia,Ana Isabel Simões Pereira, Duarte,Lídia, Gomes,Armanda V., Rodrigues,Alexandra, Basso,Ana, Reisinho,Meireles, José S.Santos-Mateus, DavidVilla de Brito, Maria TeresaLuís Manuel Morgado, Tavares,Santos-Gomes, Gda Fonseca, Isabel Pereira2021-05-01T22:47:15Z2019-10-182019-10-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article18application/pdfhttp://hdl.handle.net/10362/116591eng2297-1769PURE: 17175544https://doi.org/10.3389/fvets.2019.00362info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:59:13Zoai:run.unl.pt:10362/116591Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:43:08.762100Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
title |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
spellingShingle |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment Marcos Ferreira, Santos, Allopurinol Bone marrow Canine leishmaniosis Cytokine gene expression Lymph node Meglumine antimoniate Miltefosine Peripheral blood mononuclear cells |
title_short |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
title_full |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
title_fullStr |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
title_full_unstemmed |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
title_sort |
Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment |
author |
Marcos Ferreira, Santos, |
author_facet |
Marcos Ferreira, Santos, Graça Maria, Alexandre-Pires, Pereira, Maria A Cátia S., Marques, Gomes, Joana Jorge Jesus, Correia, Ana Isabel Simões Pereira, Duarte, Lídia, Gomes, Armanda V., Rodrigues, Alexandra, Basso, Ana, Reisinho, Meireles, José S. Santos-Mateus, David Villa de Brito, Maria Teresa Luís Manuel Morgado, Tavares, Santos-Gomes, G da Fonseca, Isabel Pereira |
author_role |
author |
author2 |
Graça Maria, Alexandre-Pires, Pereira, Maria A Cátia S., Marques, Gomes, Joana Jorge Jesus, Correia, Ana Isabel Simões Pereira, Duarte, Lídia, Gomes, Armanda V., Rodrigues, Alexandra, Basso, Ana, Reisinho, Meireles, José S. Santos-Mateus, David Villa de Brito, Maria Teresa Luís Manuel Morgado, Tavares, Santos-Gomes, G da Fonseca, Isabel Pereira |
author2_role |
author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Vector borne diseases and pathogens (VBD) Global Health and Tropical Medicine (GHTM) RUN |
dc.contributor.author.fl_str_mv |
Marcos Ferreira, Santos, Graça Maria, Alexandre-Pires, Pereira, Maria A Cátia S., Marques, Gomes, Joana Jorge Jesus, Correia, Ana Isabel Simões Pereira, Duarte, Lídia, Gomes, Armanda V., Rodrigues, Alexandra, Basso, Ana, Reisinho, Meireles, José S. Santos-Mateus, David Villa de Brito, Maria Teresa Luís Manuel Morgado, Tavares, Santos-Gomes, G da Fonseca, Isabel Pereira |
dc.subject.por.fl_str_mv |
Allopurinol Bone marrow Canine leishmaniosis Cytokine gene expression Lymph node Meglumine antimoniate Miltefosine Peripheral blood mononuclear cells |
topic |
Allopurinol Bone marrow Canine leishmaniosis Cytokine gene expression Lymph node Meglumine antimoniate Miltefosine Peripheral blood mononuclear cells |
description |
Canine leishmaniosis (CanL) caused by Leishmania infantum is a zoonotic disease of global concern. Antileishmanial drug therapies commonly used to treat sick dogs improve their clinical condition, although when discontinued relapses can occur. Thus, the current study aims to evaluate the effect of CanL treatments in peripheral blood, lymph node, and bone marrow cytokine profile associated with clinical recovery. Two groups of six dogs diagnosed with CanL were treated with miltefosine combined with allopurinol and meglumine antimoniate combined with allopurinol (MT+A and MG+A), respectively. At diagnosis and after treatment, during a 3-month follow-up, clinical signs, hematological and biochemical parameters, urinalysis results and antileishmanial antibody titers were registered. Furthermore, peripheral blood, popliteal lymph node, and bone marrow samples were collected to assess the gene expression of IL-2, IL-4, IL-5, IL-10, IL-12, TNF-α, TGF-β, and IFN-γ by qPCR. In parallel, were also evaluated samples obtained from five healthy dogs. Both treatment protocols promoted the remission of clinical signs as well as normalization of hematological and biochemical parameters and urinalysis values. Antileishmanial antibodies returned to non-significant titers in all dogs. Sick dogs showed a generalized upregulation of IFN-γ and downregulation of IL-2, IL-4, and TGF-β, while gene expression of IL-12, TNF-α, IL-5, and IL-10 varied between groups and according to evaluated tissue. A trend to the normalization of cytokine gene expression was induced by both miltefosine and meglumine antimoniate combined therapies. However, IFN-γ gene expression was still up-regulated in the three evaluated tissues. Furthermore, the effect of treatment in the gene expression of cytokines that were not significantly changed by infection, indicates that miltefosine and meglumine antimoniate combined therapy directly affects cytokine generation. Both combined therapies are effective in CanL treatment, leading to sustained pro-inflammatory immune environments that can compromise parasite survival and favor dogs' clinical cure. In the current study, anti-inflammatory and regulatory cytokines do not seem to play a prominent role in CanL or during clinical recovery. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-10-18 2019-10-18T00:00:00Z 2021-05-01T22:47:15Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/116591 |
url |
http://hdl.handle.net/10362/116591 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2297-1769 PURE: 17175544 https://doi.org/10.3389/fvets.2019.00362 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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18 application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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