Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment

Detalhes bibliográficos
Autor(a) principal: Santos, Marcos André Ferreira
Data de Publicação: 2019
Outros Autores: Alexandre-Pires, Graça, Pereira, Maria A., Marques, Cátia Filipa Saraiva, Gomes, Joana, Correia, Jorge Manuel de Jesus, Duarte, Ana, Gomes, Lídia, Rodrigues, Armanda, Basso, Alexandra, Reisinho, Ana, Meireles, José, Santos-Mateus, David, Villa Brito, Maria Teresa, Tavares, Luis, Santos-Gomes, Gabriela M., Pereira da Fonseca, Isabel
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.5/22435
Resumo: Research Areas: Veterinary Sciences
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spelling Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatmentCanine leishmaniosisperipheral blood mononuclear cellslymph nodebone marrowcytokine gene expressionmeglumine antimoniatemiltefosineallopurinolResearch Areas: Veterinary SciencesCanine 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-alpha, TGF-beta, and IFN-gamma 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-gamma and downregulation of IL-2, IL-4, and TGF-beta, while gene expression of IL-12, TNF-alpha, 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-gamma 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.Dirk Werling, Royal Veterinary College (RVC), United KingdomRepositório da Universidade de LisboaSantos, Marcos André FerreiraAlexandre-Pires, GraçaPereira, Maria A.Marques, Cátia Filipa SaraivaGomes, JoanaCorreia, Jorge Manuel de JesusDuarte, AnaGomes, LídiaRodrigues, ArmandaBasso, AlexandraReisinho, AnaMeireles, JoséSantos-Mateus, DavidVilla Brito, Maria TeresaTavares, LuisSantos-Gomes, Gabriela M.Pereira da Fonseca, Isabel2021-10-27T22:33:33Z2019-10-182019-10-18T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.5/22435engSantos MF, Alexandre-Pires G, Pereira MA, Marques CS, Gomes J, Correia J, Duarte A, Gomes L, Rodrigues AV, Basso A, et al. 2019. Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment. Frontiers in Veterinary Sciences. 6:36210.3389/fvets.2019.00362Frontiers in Veterinary Sciencesinfo: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:RCAAP2023-03-06T14:51:57Zoai:www.repository.utl.pt:10400.5/22435Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:06:51.719592Repositório 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
Santos, Marcos André Ferreira
Canine leishmaniosis
peripheral blood mononuclear cells
lymph node
bone marrow
cytokine gene expression
meglumine antimoniate
miltefosine
allopurinol
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 Santos, Marcos André Ferreira
author_facet Santos, Marcos André Ferreira
Alexandre-Pires, Graça
Pereira, Maria A.
Marques, Cátia Filipa Saraiva
Gomes, Joana
Correia, Jorge Manuel de Jesus
Duarte, Ana
Gomes, Lídia
Rodrigues, Armanda
Basso, Alexandra
Reisinho, Ana
Meireles, José
Santos-Mateus, David
Villa Brito, Maria Teresa
Tavares, Luis
Santos-Gomes, Gabriela M.
Pereira da Fonseca, Isabel
author_role author
author2 Alexandre-Pires, Graça
Pereira, Maria A.
Marques, Cátia Filipa Saraiva
Gomes, Joana
Correia, Jorge Manuel de Jesus
Duarte, Ana
Gomes, Lídia
Rodrigues, Armanda
Basso, Alexandra
Reisinho, Ana
Meireles, José
Santos-Mateus, David
Villa Brito, Maria Teresa
Tavares, Luis
Santos-Gomes, Gabriela M.
Pereira da Fonseca, Isabel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Santos, Marcos André Ferreira
Alexandre-Pires, Graça
Pereira, Maria A.
Marques, Cátia Filipa Saraiva
Gomes, Joana
Correia, Jorge Manuel de Jesus
Duarte, Ana
Gomes, Lídia
Rodrigues, Armanda
Basso, Alexandra
Reisinho, Ana
Meireles, José
Santos-Mateus, David
Villa Brito, Maria Teresa
Tavares, Luis
Santos-Gomes, Gabriela M.
Pereira da Fonseca, Isabel
dc.subject.por.fl_str_mv Canine leishmaniosis
peripheral blood mononuclear cells
lymph node
bone marrow
cytokine gene expression
meglumine antimoniate
miltefosine
allopurinol
topic Canine leishmaniosis
peripheral blood mononuclear cells
lymph node
bone marrow
cytokine gene expression
meglumine antimoniate
miltefosine
allopurinol
description Research Areas: Veterinary Sciences
publishDate 2019
dc.date.none.fl_str_mv 2019-10-18
2019-10-18T00:00:00Z
2021-10-27T22:33:33Z
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/10400.5/22435
url http://hdl.handle.net/10400.5/22435
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Santos MF, Alexandre-Pires G, Pereira MA, Marques CS, Gomes J, Correia J, Duarte A, Gomes L, Rodrigues AV, Basso A, et al. 2019. Meglumine antimoniate and miltefosine combined with allopurinol sustain pro-inflammatory immune environments during canine leishmaniosis treatment. Frontiers in Veterinary Sciences. 6:362
10.3389/fvets.2019.00362
Frontiers in Veterinary Sciences
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Dirk Werling, Royal Veterinary College (RVC), United Kingdom
publisher.none.fl_str_mv Dirk Werling, Royal Veterinary College (RVC), United Kingdom
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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