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Impact of levamisole in co-administration with benznidazole on experimental Chagas disease

Published online by Cambridge University Press:  03 May 2019

Marianne Rocha Simões-Silva ,
Raiza Brandão Peres ,
Constança Britto ,
Cynthia Machado Cascabulho ,
Gabriel de Melo Oliveira ,
Aline Nefertiti da Gama ,
Cristiane França da Silva ,
Karine Lima da Costa ,
Paula Finamore Araújo  and
Jerônimo Diego de Souza Campos
...Show all authors
Marianne Rocha Simões-Silva
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Raiza Brandão Peres
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Constança Britto
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Pavilhão Leônidas Deane, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Cynthia Machado Cascabulho
Affiliation:
Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Gabriel de Melo Oliveira
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Aline Nefertiti da Gama
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Cristiane França da Silva
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Karine Lima da Costa
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Paula Finamore Araújo
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Pavilhão Leônidas Deane, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Jerônimo Diego de Souza Campos
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Marcos Meuser Batista
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Kelly Cristina Demarque
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Otacílio da Cruz Moreira
Affiliation:
Laboratório de Biologia Molecular e Doenças Endêmicas, Pavilhão Leônidas Deane, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
Maria de Nazaré Correia Soeiro*
Affiliation:
Laboratório de Biologia Celular, Pavilhão Cardoso Fontes, Instituto Oswaldo Cruz (IOC/Fiocruz), Avenida Brasil, 4365, Manguinhos, 21040-900, Rio de Janeiro, RJ, Brazil
*
Author for correspondence: Maria de Nazaré Correia Soeiro, E-mail: [email protected]
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Abstract

Levamisole (Lms) is an anthelminthic drug with immunomodulatory activity. Chagas disease (CD) is caused by Trypanosoma cruzi and there is very low access to the drugs available, benznidazole (Bz) and nifurtimox, both far from ideal. In a drug-repurposing strategy to test potential activity as antiparasitic and immunomodulatory agent for CD, Lms was assayed on acute T. cruzi murine infection, alone and in co-administration with Bz. During protocol standardization, 100 and 10 mpk of Bz given for five consecutive days resulted in parasitaemia suppression and 100% animal survival only with the highest dose. Flow cytometry showed that both optimal (100 mpk) and suboptimal (10 mpk) doses of Bz equally decreased the plasma levels of cytokines commonly elevated in this acute infection model. Lms alone (10–0.5 mpk) did not decrease parasitaemia nor mortality rates. Co-administration was investigated using the suboptimal dose of Bz and different doses of Lms. While Bz 10 mpk did not alter parasitaemia, the combo partially reduced it but only slightly promoted animal survival. This effect could be related to Th1-response modulation since interleukin-6 and interferon-γ were higher after treatment with the combo.

Keywords

Chagas diseasedrug co-administrationimmunomodulationlevamisole
Type
Research Article
Information
Parasitology , Volume 146 , Issue 8 , July 2019 , pp. 1055 - 1062
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Copyright
Copyright © Cambridge University Press 2019 

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