Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids

Autores
Córdoba Moreno, Marlina Olyissa; Todero, Maria Florencia; Fontanals, Adriana Mirta; Pineda, Gonzalo Ezequiel; Montagna, Daniela Romina; Yokobori, Noemí; Ramos, Maria Victoria; Barrientos, Gabriela Laura; Toblli, Jorge Eduardo; Isturiz, Martín Amadeo; Rearte, María Bárbara
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxic shock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.
Fil: Córdoba Moreno, Marlina Olyissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fontanals, Adriana Mirta. Fundación Instituto Leloir; Argentina
Fil: Pineda, Gonzalo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Montagna, Daniela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Barrientos, Gabriela Laura. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Materia
ENDOTOXIN TOLERANCE
GLUCOCORTICOIDS
LPS
SEPSIS
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:11336/95959
Acceder
id CONICETDig_f376af8678c1e3bd59580dcf10ee69cb
oai_identifier_str oai:ri.conicet.gov.ar:11336/95959
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With GlucocorticoidsCórdoba Moreno, Marlina OlyissaTodero, Maria FlorenciaFontanals, Adriana MirtaPineda, Gonzalo EzequielMontagna, Daniela RominaYokobori, NoemíRamos, Maria VictoriaBarrientos, Gabriela LauraToblli, Jorge EduardoIsturiz, Martín AmadeoRearte, María BárbaraENDOTOXIN TOLERANCEGLUCOCORTICOIDSLPSSEPSIShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Sepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxic shock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.Fil: Córdoba Moreno, Marlina Olyissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Fontanals, Adriana Mirta. Fundación Instituto Leloir; ArgentinaFil: Pineda, Gonzalo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Montagna, Daniela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Barrientos, Gabriela Laura. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaLippincott Williams2019-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95959Córdoba Moreno, Marlina Olyissa; Todero, Maria Florencia; Fontanals, Adriana Mirta; Pineda, Gonzalo Ezequiel; Montagna, Daniela Romina; et al.; Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids; Lippincott Williams; Shock; 52; 2; 8-2019; 264-2731073-23221540-0514CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://Insights.ovid.com/crossref?an=00024382-900000000-97789info:eu-repo/semantics/altIdentifier/doi/10.1097/SHK.0000000000001233info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:10:10Zoai:ri.conicet.gov.ar:11336/95959instacron: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:34982025-09-03 10:10:11.303CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
title Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
spellingShingle Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
Córdoba Moreno, Marlina Olyissa
ENDOTOXIN TOLERANCE
GLUCOCORTICOIDS
LPS
SEPSIS
title_short Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
title_full Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
title_fullStr Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
title_full_unstemmed Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
title_sort Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids
dc.creator.none.fl_str_mv Córdoba Moreno, Marlina Olyissa
Todero, Maria Florencia
Fontanals, Adriana Mirta
Pineda, Gonzalo Ezequiel
Montagna, Daniela Romina
Yokobori, Noemí
Ramos, Maria Victoria
Barrientos, Gabriela Laura
Toblli, Jorge Eduardo
Isturiz, Martín Amadeo
Rearte, María Bárbara
author Córdoba Moreno, Marlina Olyissa
author_facet Córdoba Moreno, Marlina Olyissa
Todero, Maria Florencia
Fontanals, Adriana Mirta
Pineda, Gonzalo Ezequiel
Montagna, Daniela Romina
Yokobori, Noemí
Ramos, Maria Victoria
Barrientos, Gabriela Laura
Toblli, Jorge Eduardo
Isturiz, Martín Amadeo
Rearte, María Bárbara
author_role author
author2 Todero, Maria Florencia
Fontanals, Adriana Mirta
Pineda, Gonzalo Ezequiel
Montagna, Daniela Romina
Yokobori, Noemí
Ramos, Maria Victoria
Barrientos, Gabriela Laura
Toblli, Jorge Eduardo
Isturiz, Martín Amadeo
Rearte, María Bárbara
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ENDOTOXIN TOLERANCE
GLUCOCORTICOIDS
LPS
SEPSIS
topic ENDOTOXIN TOLERANCE
GLUCOCORTICOIDS
LPS
SEPSIS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Sepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxic shock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.
Fil: Córdoba Moreno, Marlina Olyissa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Todero, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Fontanals, Adriana Mirta. Fundación Instituto Leloir; Argentina
Fil: Pineda, Gonzalo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Montagna, Daniela Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Yokobori, Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Ramos, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Barrientos, Gabriela Laura. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Isturiz, Martín Amadeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Rearte, María Bárbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
description Sepsis constitutes one of the major causes of death in ICUs. In sepsis induced by gram-negative, although lipopolysaccharide (LPS) initially induces an exacerbated secretion of proinflammatory cytokines leading to endotoxic shock and death resembling a septic shock, it is also capable of inducing refractoriness to subsequent challenge with LPS, a state known as endotoxin tolerance, which is considered the initial step of the immunosuppression found in septic patients. As we previously demonstrated the importance of glucocorticoids in endotoxin tolerance, the aim of this study was to evaluate the contribution of Interleukin-10 (IL-10) both in the endotoxic shock and in the development of the tolerance and its relationship with glucocorticoids. Our results show that, upon LPS challenge, IL-10 knockout mice (KO) mice had an enhanced LPS sensitivity, along with elevated levels of proinflammatory cytokines as tumor necrosis factor-α, IL-12 and interferon-γ, and enhanced tissue damage, despite the high levels of glucocorticoids. This effect may be because, in part, of the higher expression of tumor necrosis factor receptors in IL-10 KO mice. Further, the injection of dexamethasone did not protect IL-10 KO mice from a LPS lethal challenge. Although tolerance was achieved in the absence of IL-10, it was weaker and the elevated levels of glucocorticoids were not able to reverse the high sensitivity of IL-10 KO mice to LPS. Nevertheless, glucocorticoids would play a pivotal role in the establishment and maintenance of this partial tolerance in IL-10 KO mice. Finally, our results show that IL-10 and glucocorticoids could act in a bidirectional way influencing the inflammatory and anti-inflammatory periods.
publishDate 2019
dc.date.none.fl_str_mv 2019-08
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/11336/95959
Córdoba Moreno, Marlina Olyissa; Todero, Maria Florencia; Fontanals, Adriana Mirta; Pineda, Gonzalo Ezequiel; Montagna, Daniela Romina; et al.; Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids; Lippincott Williams; Shock; 52; 2; 8-2019; 264-273
1073-2322
1540-0514
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95959
identifier_str_mv Córdoba Moreno, Marlina Olyissa; Todero, Maria Florencia; Fontanals, Adriana Mirta; Pineda, Gonzalo Ezequiel; Montagna, Daniela Romina; et al.; Consequences of the Lack of IL-10 in Different Endotoxin Effects and its Relationship With Glucocorticoids; Lippincott Williams; Shock; 52; 2; 8-2019; 264-273
1073-2322
1540-0514
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://Insights.ovid.com/crossref?an=00024382-900000000-97789
info:eu-repo/semantics/altIdentifier/doi/10.1097/SHK.0000000000001233
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
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dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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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