Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock

Autores
Mul Fedele, Malena Lis; Aiello, Ignacio; Caldart, Carlos Sebastián; Golombek, Diego Andrés; Marpegan, Luciano; Paladino, Natalia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sepsis is caused by a dysregulated host response to infection, and characterized by uncontrolled inflammation together with immunosuppression, impaired innate immune functions of phagocytes and complement activation. Septic patients develop fever or hypothermia, being the last one characteristic of severe cases. Both lipopolysaccharide (LPS) and Tumor Necrosis Factor (TNF)-α- induced septic shock in mice is dependent on the time of administration. In this study, we aimed to further characterize the circadian response to high doses of LPS. First, we found that mice injected with LPS at ZT11 developed a higher hypothermia than those inoculated at ZT19. This response was accompanied by higher neuronal activation of the preoptic, suprachiasmatic, and paraventricular nuclei of the hypothalamus. However, LPS-induced Tnf-α and Tnf-α type 1 receptor (TNFR1) expression in the preoptic area was time-independent. We also analyzed peritoneal and spleen macrophages, and observed an exacerbated response after ZT11 stimulation. The serum of mice inoculated with LPS at ZT11 induced deeper hypothermia in naïve animals than the one coming from ZT19-inoculated mice, related to higher TNF-α serum levels during the day. We also analyzed the response in TNFR1-deficient mice, and found that both the daily difference in the mortality rate, the hypothermic response and neuronal activation were lost. Moreover, mice subjected to circadian desynchronization showed no differences in the mortality rate throughout the day, and developed lower minimum temperatures than mice under light-dark conditions. Also, those injected at ZT11 showed increased levels of TNF-α in serum compared to standard light conditions. These results suggest a circadian dependency of the central thermoregulatory and peripheral inflammatory response to septic-shock, with TNF-α playing a central role in this circadian response.
Fil: Mul Fedele, Malena Lis. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Aiello, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Caldart, Carlos Sebastián. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Marpegan, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Paladino, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Materia
CIRCADIAN RHYTHMS
HYPOTHERMIA
IMMUNE SYSTEM
SEPSIS
TUMOR NECROSIS FACTOR-Α
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:11336/141574
Acceder
id CONICETDig_1476f11c71049c24d6cf65d45949e0c6
oai_identifier_str oai:ri.conicet.gov.ar:11336/141574
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic ShockMul Fedele, Malena LisAiello, IgnacioCaldart, Carlos SebastiánGolombek, Diego AndrésMarpegan, LucianoPaladino, NataliaCIRCADIAN RHYTHMSHYPOTHERMIAIMMUNE SYSTEMSEPSISTUMOR NECROSIS FACTOR-Αhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Sepsis is caused by a dysregulated host response to infection, and characterized by uncontrolled inflammation together with immunosuppression, impaired innate immune functions of phagocytes and complement activation. Septic patients develop fever or hypothermia, being the last one characteristic of severe cases. Both lipopolysaccharide (LPS) and Tumor Necrosis Factor (TNF)-α- induced septic shock in mice is dependent on the time of administration. In this study, we aimed to further characterize the circadian response to high doses of LPS. First, we found that mice injected with LPS at ZT11 developed a higher hypothermia than those inoculated at ZT19. This response was accompanied by higher neuronal activation of the preoptic, suprachiasmatic, and paraventricular nuclei of the hypothalamus. However, LPS-induced Tnf-α and Tnf-α type 1 receptor (TNFR1) expression in the preoptic area was time-independent. We also analyzed peritoneal and spleen macrophages, and observed an exacerbated response after ZT11 stimulation. The serum of mice inoculated with LPS at ZT11 induced deeper hypothermia in naïve animals than the one coming from ZT19-inoculated mice, related to higher TNF-α serum levels during the day. We also analyzed the response in TNFR1-deficient mice, and found that both the daily difference in the mortality rate, the hypothermic response and neuronal activation were lost. Moreover, mice subjected to circadian desynchronization showed no differences in the mortality rate throughout the day, and developed lower minimum temperatures than mice under light-dark conditions. Also, those injected at ZT11 showed increased levels of TNF-α in serum compared to standard light conditions. These results suggest a circadian dependency of the central thermoregulatory and peripheral inflammatory response to septic-shock, with TNF-α playing a central role in this circadian response.Fil: Mul Fedele, Malena Lis. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aiello, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Caldart, Carlos Sebastián. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Marpegan, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFil: Paladino, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; ArgentinaFrontiers Media S.A.2020-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/141574Mul Fedele, Malena Lis; Aiello, Ignacio; Caldart, Carlos Sebastián; Golombek, Diego Andrés; Marpegan, Luciano; et al.; Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock; Frontiers Media S.A.; Frontiers in Cellular and Infection Microbiology; 10; 3-2020; 1-182235-2988CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fcimb.2020.00100/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2020.00100info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:07:25Zoai:ri.conicet.gov.ar:11336/141574instacron: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 10:07:25.835CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
title Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
spellingShingle Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
Mul Fedele, Malena Lis
CIRCADIAN RHYTHMS
HYPOTHERMIA
IMMUNE SYSTEM
SEPSIS
TUMOR NECROSIS FACTOR-Α
title_short Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
title_full Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
title_fullStr Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
title_full_unstemmed Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
title_sort Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock
dc.creator.none.fl_str_mv Mul Fedele, Malena Lis
Aiello, Ignacio
Caldart, Carlos Sebastián
Golombek, Diego Andrés
Marpegan, Luciano
Paladino, Natalia
author Mul Fedele, Malena Lis
author_facet Mul Fedele, Malena Lis
Aiello, Ignacio
Caldart, Carlos Sebastián
Golombek, Diego Andrés
Marpegan, Luciano
Paladino, Natalia
author_role author
author2 Aiello, Ignacio
Caldart, Carlos Sebastián
Golombek, Diego Andrés
Marpegan, Luciano
Paladino, Natalia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CIRCADIAN RHYTHMS
HYPOTHERMIA
IMMUNE SYSTEM
SEPSIS
TUMOR NECROSIS FACTOR-Α
topic CIRCADIAN RHYTHMS
HYPOTHERMIA
IMMUNE SYSTEM
SEPSIS
TUMOR NECROSIS FACTOR-Α
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Sepsis is caused by a dysregulated host response to infection, and characterized by uncontrolled inflammation together with immunosuppression, impaired innate immune functions of phagocytes and complement activation. Septic patients develop fever or hypothermia, being the last one characteristic of severe cases. Both lipopolysaccharide (LPS) and Tumor Necrosis Factor (TNF)-α- induced septic shock in mice is dependent on the time of administration. In this study, we aimed to further characterize the circadian response to high doses of LPS. First, we found that mice injected with LPS at ZT11 developed a higher hypothermia than those inoculated at ZT19. This response was accompanied by higher neuronal activation of the preoptic, suprachiasmatic, and paraventricular nuclei of the hypothalamus. However, LPS-induced Tnf-α and Tnf-α type 1 receptor (TNFR1) expression in the preoptic area was time-independent. We also analyzed peritoneal and spleen macrophages, and observed an exacerbated response after ZT11 stimulation. The serum of mice inoculated with LPS at ZT11 induced deeper hypothermia in naïve animals than the one coming from ZT19-inoculated mice, related to higher TNF-α serum levels during the day. We also analyzed the response in TNFR1-deficient mice, and found that both the daily difference in the mortality rate, the hypothermic response and neuronal activation were lost. Moreover, mice subjected to circadian desynchronization showed no differences in the mortality rate throughout the day, and developed lower minimum temperatures than mice under light-dark conditions. Also, those injected at ZT11 showed increased levels of TNF-α in serum compared to standard light conditions. These results suggest a circadian dependency of the central thermoregulatory and peripheral inflammatory response to septic-shock, with TNF-α playing a central role in this circadian response.
Fil: Mul Fedele, Malena Lis. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Aiello, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Caldart, Carlos Sebastián. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Golombek, Diego Andrés. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Marpegan, Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
Fil: Paladino, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Cronobiología; Argentina
description Sepsis is caused by a dysregulated host response to infection, and characterized by uncontrolled inflammation together with immunosuppression, impaired innate immune functions of phagocytes and complement activation. Septic patients develop fever or hypothermia, being the last one characteristic of severe cases. Both lipopolysaccharide (LPS) and Tumor Necrosis Factor (TNF)-α- induced septic shock in mice is dependent on the time of administration. In this study, we aimed to further characterize the circadian response to high doses of LPS. First, we found that mice injected with LPS at ZT11 developed a higher hypothermia than those inoculated at ZT19. This response was accompanied by higher neuronal activation of the preoptic, suprachiasmatic, and paraventricular nuclei of the hypothalamus. However, LPS-induced Tnf-α and Tnf-α type 1 receptor (TNFR1) expression in the preoptic area was time-independent. We also analyzed peritoneal and spleen macrophages, and observed an exacerbated response after ZT11 stimulation. The serum of mice inoculated with LPS at ZT11 induced deeper hypothermia in naïve animals than the one coming from ZT19-inoculated mice, related to higher TNF-α serum levels during the day. We also analyzed the response in TNFR1-deficient mice, and found that both the daily difference in the mortality rate, the hypothermic response and neuronal activation were lost. Moreover, mice subjected to circadian desynchronization showed no differences in the mortality rate throughout the day, and developed lower minimum temperatures than mice under light-dark conditions. Also, those injected at ZT11 showed increased levels of TNF-α in serum compared to standard light conditions. These results suggest a circadian dependency of the central thermoregulatory and peripheral inflammatory response to septic-shock, with TNF-α playing a central role in this circadian response.
publishDate 2020
dc.date.none.fl_str_mv 2020-03
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/11336/141574
Mul Fedele, Malena Lis; Aiello, Ignacio; Caldart, Carlos Sebastián; Golombek, Diego Andrés; Marpegan, Luciano; et al.; Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock; Frontiers Media S.A.; Frontiers in Cellular and Infection Microbiology; 10; 3-2020; 1-18
2235-2988
CONICET Digital
CONICET
url http://hdl.handle.net/11336/141574
identifier_str_mv Mul Fedele, Malena Lis; Aiello, Ignacio; Caldart, Carlos Sebastián; Golombek, Diego Andrés; Marpegan, Luciano; et al.; Differential Thermoregulatory and Inflammatory Patterns in the Circadian Response to LPS-Induced Septic Shock; Frontiers Media S.A.; Frontiers in Cellular and Infection Microbiology; 10; 3-2020; 1-18
2235-2988
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fcimb.2020.00100/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fcimb.2020.00100
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
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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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score 13.13397

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