Dataset Information

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 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.

SUBMITTER: Joachim R

PROVIDER: S-EPMC5707402 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Characterising Pre-pubertal Resistance to Death from Endotoxemia.

Joachim Rose R Suber Freeman F Kobzik Lester L

Scientific reports 20171129 1

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 ...[more]

PMID: 29185479

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Project description:Childhood obesity prevalence has increased over the last 30 years. The Heart Rate Variability (HRV) studies performed in adults suggest a possible relation between abnormal autonomic regulation and hypertension in the situation of overweight or obesity. Objective: The aims of this study were to explore the early relationships between adiposity and blood pressure and HRV in pre-pubertal children. Methods: Data were collected during the medical examination of the follow-up at 7 years of the TIMOUN mother-child cohort in Guadeloupe. Body Mass Index z-score (zBMI), sum of tricipital and subscapular skinfold thickness, percentage of fat mass, and Waist-to-Height Ratio were measured. A global corpulence score was computed using a Principal Component Analysis (PCA). Systolic Blood Pressure (SBP) and HRV parameters (cardiac holter monitoring) were collected under 2 conditions (calm and tachycardial period). Relations between HRV, SBP, each adiposity indicator and the corpulence score were studied with restricted cubic splines models, and linear regression models. The age at adiposity rebound (AR) was estimated from the individual growth curves. Results: 575 children were included in the SBP study (mean age: 7.7 years, from 85 to 99 months). SBP was linearly correlated with the corpulence score and the zBMI. An increase of 1 in the zBMI was associated with an increase of 2.3 (±0.28) mmHg in SBP. The effect-size of zBMI on SBP was higher in children with early age at AR. Compared to children with normal BMI, children with a zBMI <™2SD had their RMSSD, SDNN, LF and HF indicators in tachycardial conditions significantly reduced by -30, -21, -37, and -48%, respectively. In boys with a zBMI >2SD, we observed a global increase in all HRV parameters (under tachycardial conditions), particularly the LF [β = 0.43 (±0.18)]. Conclusion: In pre-pubertal period a positive correlation between adiposity excess and SBP was observed with significant changes of HRV in boys, arguing for an early abnormal autonomic regulation and for early preventive intervention in the infancy period, particularly in case of overweight or obesity. Thinness was associated with a reduction in almost all the HRV parameters studied, when compared to normal corpulence, suggesting a decrease in autonomic influence.

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Characterising Pre-pubertal Resistance to Death from Endotoxemia.

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Characterising Pre-pubertal Resistance to Death from Endotoxemia.

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