Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

Abstract Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effect...

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Autores principales:	Alexandre Chagas Santana, Wellington Andraus, Filipe Miranda Oliveira Silva, Humberto Dellê, Rafael Pepineli, Edvaldo Leal de Moraes, Cristoforo Scavone, Larissa de Sá Lima, Sabrina Degaspari, Sergio Brasil, Davi Jorge Fontoura Solla, Liliane Moreira Ruiz, Karina Andrighetti de Oliveira-Braga, Natalia Aparecida Nepomuceno, Paulo Manuel Pêgo-Fernandes, Stefan Gunther Tullius, Eberval Gadelha Figueiredo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c377023aeb3c49e0bf911f268d1c356c
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spelling	oai:doaj.org-article:c377023aeb3c49e0bf911f268d1c356c2021-12-02T18:51:07ZImmunomodulatory effects of thalidomide in an experimental brain death liver donor model10.1038/s41598-021-98538-z2045-2322https://doaj.org/article/c377023aeb3c49e0bf911f268d1c356c2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98538-zhttps://doaj.org/toc/2045-2322Abstract Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-β, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-β, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.Alexandre Chagas SantanaWellington AndrausFilipe Miranda Oliveira SilvaHumberto DellêRafael PepineliEdvaldo Leal de MoraesCristoforo ScavoneLarissa de Sá LimaSabrina DegaspariSergio BrasilDavi Jorge Fontoura SollaLiliane Moreira RuizKarina Andrighetti de Oliveira-BragaNatalia Aparecida NepomucenoPaulo Manuel Pêgo-FernandesStefan Gunther TulliusEberval Gadelha FigueiredoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexandre Chagas Santana Wellington Andraus Filipe Miranda Oliveira Silva Humberto Dellê Rafael Pepineli Edvaldo Leal de Moraes Cristoforo Scavone Larissa de Sá Lima Sabrina Degaspari Sergio Brasil Davi Jorge Fontoura Solla Liliane Moreira Ruiz Karina Andrighetti de Oliveira-Braga Natalia Aparecida Nepomuceno Paulo Manuel Pêgo-Fernandes Stefan Gunther Tullius Eberval Gadelha Figueiredo Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
description	Abstract Brain death is characterized by a generalized inflammatory response that results in multiorgan damage. This process is mainly mediated through cytokines, which amplify graft immunogenicity. We investigated the immunological response in a brain death liver donor model and analysed the effects of thalidomide, a drug with powerful immunomodulatory properties. Brain death was induced in male Lewis rats. We studied three groups: Control (sham-operated rats in which trepanation was performed without inserting the balloon catheter), BD (rats subjected to brain death by increasing intracranial pressure) and BD + Thalid (BD rats receiving thalidomide after brain death). After 6 h, serum levels of AST, ALT, LDH, and ALP as well as systemic and hepatic levels of TNF-α, IL1-β, IL-6, and IL-10 were analysed. We also determined the mRNA expression of MHC Class I and Class II, NF-κB, and macrophage infiltration. NF-κB was also examined by electrophoretic mobility shift assay. Thalidomide treatment significantly reduced serum levels of hepatic enzymes and TNF-α, IL-1-β, and IL-6. These cytokines were evaluated at either the mRNA expression or protein level in liver tissue. In addition, thalidomide administration resulted in a significant reduction in macrophages, MHC Class I and Class II, and NF-κB activation. This study reveals that thalidomide significantly inhibited the immunologic response and graft immunogenicity, possibly through suppression of NF-κB activation.
format	article
author	Alexandre Chagas Santana Wellington Andraus Filipe Miranda Oliveira Silva Humberto Dellê Rafael Pepineli Edvaldo Leal de Moraes Cristoforo Scavone Larissa de Sá Lima Sabrina Degaspari Sergio Brasil Davi Jorge Fontoura Solla Liliane Moreira Ruiz Karina Andrighetti de Oliveira-Braga Natalia Aparecida Nepomuceno Paulo Manuel Pêgo-Fernandes Stefan Gunther Tullius Eberval Gadelha Figueiredo
author_facet	Alexandre Chagas Santana Wellington Andraus Filipe Miranda Oliveira Silva Humberto Dellê Rafael Pepineli Edvaldo Leal de Moraes Cristoforo Scavone Larissa de Sá Lima Sabrina Degaspari Sergio Brasil Davi Jorge Fontoura Solla Liliane Moreira Ruiz Karina Andrighetti de Oliveira-Braga Natalia Aparecida Nepomuceno Paulo Manuel Pêgo-Fernandes Stefan Gunther Tullius Eberval Gadelha Figueiredo
author_sort	Alexandre Chagas Santana
title	Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
title_short	Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
title_full	Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
title_fullStr	Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
title_full_unstemmed	Immunomodulatory effects of thalidomide in an experimental brain death liver donor model
title_sort	immunomodulatory effects of thalidomide in an experimental brain death liver donor model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c377023aeb3c49e0bf911f268d1c356c
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Immunomodulatory effects of thalidomide in an experimental brain death liver donor model

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