Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance

Autores
Rearte, María Bárbara; Landoni, Verónica Inés; Laborde, Evangelina Andrea; Fernández, Gabriela Cristina; Isturiz, Martín Amadeo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gram-negative infections can result in endotoxic shock, which is the most common cause of death in intensive care units. Most of the undesirable effects in sepsis and septic shock have been ascribed to lipopolysaccharide (LPS), a normal constituent of the bacterial wall. The response to LPS involves rapid secretion of proinflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, interferon-γ] and the concomitant induction of anti-inflammatory mediators such as IL-10 and transforming growth factor-β and glucocorticoids (GC), which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the principal cause of the non-specific immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that while the maintenance of tolerance is dependent upon GC, the establishment of tolerance by LPS could be inhibited by dexamethasone (Dex), a synthetic GC. Conversely, we demonstrated that mifepristone (RU486), a known GC receptor antagonist, was capable of inducing a transient and reversible disruption of endotoxin tolerance, also permitting partial restoration of the humoral immune response in LPS tolerant/immunosuppressed mice. These results are encouraging for the management of immunosuppression in sepsis and/or non-infectious shock, and deserve further investigation in the future. © 2009 British Society for Immunology.
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Fil: Laborde, Evangelina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Fil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematológicas ; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematológicas ; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Materia
Dexamethasone
Endotoxin Tolerance
Glucocorticoids
Lps
Ru486
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54506
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/54506
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential effects of glucocorticoids in the establishment and maintenance of endotoxin toleranceRearte, María BárbaraLandoni, Verónica InésLaborde, Evangelina AndreaFernández, Gabriela CristinaIsturiz, Martín AmadeoDexamethasoneEndotoxin ToleranceGlucocorticoidsLpsRu486https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Gram-negative infections can result in endotoxic shock, which is the most common cause of death in intensive care units. Most of the undesirable effects in sepsis and septic shock have been ascribed to lipopolysaccharide (LPS), a normal constituent of the bacterial wall. The response to LPS involves rapid secretion of proinflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, interferon-γ] and the concomitant induction of anti-inflammatory mediators such as IL-10 and transforming growth factor-β and glucocorticoids (GC), which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the principal cause of the non-specific immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that while the maintenance of tolerance is dependent upon GC, the establishment of tolerance by LPS could be inhibited by dexamethasone (Dex), a synthetic GC. Conversely, we demonstrated that mifepristone (RU486), a known GC receptor antagonist, was capable of inducing a transient and reversible disruption of endotoxin tolerance, also permitting partial restoration of the humoral immune response in LPS tolerant/immunosuppressed mice. These results are encouraging for the management of immunosuppression in sepsis and/or non-infectious shock, and deserve further investigation in the future. © 2009 British Society for Immunology.Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; ArgentinaFil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; ArgentinaFil: Laborde, Evangelina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; ArgentinaFil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematológicas ; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematológicas ; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; ArgentinaWiley Blackwell Publishing, Inc2010-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54506Rearte, María Bárbara; Landoni, Verónica Inés; Laborde, Evangelina Andrea; Fernández, Gabriela Cristina; Isturiz, Martín Amadeo; Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 159; 2; 2-2010; 208-2160009-9104CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2249.2009.04052.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2249.2009.04052.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:41:55Zoai:ri.conicet.gov.ar:11336/54506instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 11:41:56.423CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
title Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
spellingShingle Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
Rearte, María Bárbara
Dexamethasone
Endotoxin Tolerance
Glucocorticoids
Lps
Ru486
title_short Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
title_full Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
title_fullStr Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
title_full_unstemmed Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
title_sort Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance
dc.creator.none.fl_str_mv Rearte, María Bárbara
Landoni, Verónica Inés
Laborde, Evangelina Andrea
Fernández, Gabriela Cristina
Isturiz, Martín Amadeo
author Rearte, María Bárbara
author_facet Rearte, María Bárbara
Landoni, Verónica Inés
Laborde, Evangelina Andrea
Fernández, Gabriela Cristina
Isturiz, Martín Amadeo
author_role author
author2 Landoni, Verónica Inés
Laborde, Evangelina Andrea
Fernández, Gabriela Cristina
Isturiz, Martín Amadeo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Dexamethasone
Endotoxin Tolerance
Glucocorticoids
Lps
Ru486
topic Dexamethasone
Endotoxin Tolerance
Glucocorticoids
Lps
Ru486
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Gram-negative infections can result in endotoxic shock, which is the most common cause of death in intensive care units. Most of the undesirable effects in sepsis and septic shock have been ascribed to lipopolysaccharide (LPS), a normal constituent of the bacterial wall. The response to LPS involves rapid secretion of proinflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, interferon-γ] and the concomitant induction of anti-inflammatory mediators such as IL-10 and transforming growth factor-β and glucocorticoids (GC), which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the principal cause of the non-specific immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that while the maintenance of tolerance is dependent upon GC, the establishment of tolerance by LPS could be inhibited by dexamethasone (Dex), a synthetic GC. Conversely, we demonstrated that mifepristone (RU486), a known GC receptor antagonist, was capable of inducing a transient and reversible disruption of endotoxin tolerance, also permitting partial restoration of the humoral immune response in LPS tolerant/immunosuppressed mice. These results are encouraging for the management of immunosuppression in sepsis and/or non-infectious shock, and deserve further investigation in the future. © 2009 British Society for Immunology.
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Fil: Landoni, Verónica Inés. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Fil: Laborde, Evangelina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
Fil: Fernández, Gabriela Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematológicas ; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Invest. Hematológicas ; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Leucemia Experimental; Argentina
description Gram-negative infections can result in endotoxic shock, which is the most common cause of death in intensive care units. Most of the undesirable effects in sepsis and septic shock have been ascribed to lipopolysaccharide (LPS), a normal constituent of the bacterial wall. The response to LPS involves rapid secretion of proinflammatory cytokines [tumour necrosis factor-α, interleukin (IL)-1, IL-6, IL-8, interferon-γ] and the concomitant induction of anti-inflammatory mediators such as IL-10 and transforming growth factor-β and glucocorticoids (GC), which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the principal cause of the non-specific immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that while the maintenance of tolerance is dependent upon GC, the establishment of tolerance by LPS could be inhibited by dexamethasone (Dex), a synthetic GC. Conversely, we demonstrated that mifepristone (RU486), a known GC receptor antagonist, was capable of inducing a transient and reversible disruption of endotoxin tolerance, also permitting partial restoration of the humoral immune response in LPS tolerant/immunosuppressed mice. These results are encouraging for the management of immunosuppression in sepsis and/or non-infectious shock, and deserve further investigation in the future. © 2009 British Society for Immunology.
publishDate 2010
dc.date.none.fl_str_mv 2010-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54506
Rearte, María Bárbara; Landoni, Verónica Inés; Laborde, Evangelina Andrea; Fernández, Gabriela Cristina; Isturiz, Martín Amadeo; Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 159; 2; 2-2010; 208-216
0009-9104
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54506
identifier_str_mv Rearte, María Bárbara; Landoni, Verónica Inés; Laborde, Evangelina Andrea; Fernández, Gabriela Cristina; Isturiz, Martín Amadeo; Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance; Wiley Blackwell Publishing, Inc; Clinical and Experimental Immunology; 159; 2; 2-2010; 208-216
0009-9104
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2249.2009.04052.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2249.2009.04052.x
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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