Characterising Pre-pubertal Resistance to Death from Endotoxemia

Abstract Sepsis is a common and deadly syndrome in which a dysregulated host response to infection causes organ failure and death. The current lack of treatment options suggests that a new approach to studying sepsis is needed. Pre-pubertal children show a relative resistance to death from severe in...

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Autores principales:	Rose Joachim, Freeman Suber, Lester Kobzik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/35ec7a76c30243c6bb483aa09bd8913a
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spelling	oai:doaj.org-article:35ec7a76c30243c6bb483aa09bd8913a2021-12-02T15:06:10ZCharacterising Pre-pubertal Resistance to Death from Endotoxemia10.1038/s41598-017-16743-12045-2322https://doaj.org/article/35ec7a76c30243c6bb483aa09bd8913a2017-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-16743-1https://doaj.org/toc/2045-2322Abstract Sepsis is a common and deadly syndrome in which a dysregulated host response to infection causes organ failure and death. The current lack of treatment options suggests that a new approach to studying sepsis is needed. Pre-pubertal children show a relative resistance to death from severe infections and sepsis. To explore this phenomenon experimentally, we used an endotoxemia model of sepsis in mice. Following intra-peritoneal injection of endotoxin, pre-pubertal mice showed greater survival than post-pubertal mice (76.3% vs. 28.6%), despite exhibiting a similar degree of inflammation after two hours. Age-associated differences in the inflammatory response only became evident at twenty hours, when post-pubertal mice showed prolonged elevation of serum cytokines and differential recruitment of peritoneal immune cells. Mechanistically, prevention of puberty by hormonal blockade or acceleration of puberty by oestrogen treatment led to increased or decreased survival from endotoxemia, respectively. Additionally, the adoptive transfer of pre-pubertal peritoneal cells improved the survival of post-pubertal recipient mice, while post-pubertal peritoneal cells or vehicle did not. These data establish a model for studying childhood resistance to mortality from endotoxemia, demonstrate that oestrogen is responsible for an increased susceptibility to mortality after puberty, and identify peritoneal cells as mediators of pre-pubertal resistance.Rose JoachimFreeman SuberLester KobzikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rose Joachim Freeman Suber Lester Kobzik Characterising Pre-pubertal Resistance to Death from Endotoxemia
description	Abstract Sepsis is a common and deadly syndrome in which a dysregulated host response to infection causes organ failure and death. The current lack of treatment options suggests that a new approach to studying sepsis is needed. Pre-pubertal children show a relative resistance to death from severe infections and sepsis. To explore this phenomenon experimentally, we used an endotoxemia model of sepsis in mice. Following intra-peritoneal injection of endotoxin, pre-pubertal mice showed greater survival than post-pubertal mice (76.3% vs. 28.6%), despite exhibiting a similar degree of inflammation after two hours. Age-associated differences in the inflammatory response only became evident at twenty hours, when post-pubertal mice showed prolonged elevation of serum cytokines and differential recruitment of peritoneal immune cells. Mechanistically, prevention of puberty by hormonal blockade or acceleration of puberty by oestrogen treatment led to increased or decreased survival from endotoxemia, respectively. Additionally, the adoptive transfer of pre-pubertal peritoneal cells improved the survival of post-pubertal recipient mice, while post-pubertal peritoneal cells or vehicle did not. These data establish a model for studying childhood resistance to mortality from endotoxemia, demonstrate that oestrogen is responsible for an increased susceptibility to mortality after puberty, and identify peritoneal cells as mediators of pre-pubertal resistance.
format	article
author	Rose Joachim Freeman Suber Lester Kobzik
author_facet	Rose Joachim Freeman Suber Lester Kobzik
author_sort	Rose Joachim
title	Characterising Pre-pubertal Resistance to Death from Endotoxemia
title_short	Characterising Pre-pubertal Resistance to Death from Endotoxemia
title_full	Characterising Pre-pubertal Resistance to Death from Endotoxemia
title_fullStr	Characterising Pre-pubertal Resistance to Death from Endotoxemia
title_full_unstemmed	Characterising Pre-pubertal Resistance to Death from Endotoxemia
title_sort	characterising pre-pubertal resistance to death from endotoxemia
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/35ec7a76c30243c6bb483aa09bd8913a
work_keys_str_mv	AT rosejoachim characterisingprepubertalresistancetodeathfromendotoxemia AT freemansuber characterisingprepubertalresistancetodeathfromendotoxemia AT lesterkobzik characterisingprepubertalresistancetodeathfromendotoxemia
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Characterising Pre-pubertal Resistance to Death from Endotoxemia

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