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Intensive Care Medicine
Published in: Intensive Care Medicine 1/2010

01-01-2010 | Pediatric Original

Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock

Authors: Jennifer M. Kaplan, Alvin Denenberg, Marie Monaco, Marchele Nowell, Hector Wong, Basilia Zingarelli

Published in: Intensive Care Medicine | Issue 1/2010

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Abstract

Purpose

To assess changes in peroxisome proliferator-activated receptor-γ (PPARγ) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARγ, 15-deoxy-∆12,14-PGJ2 (15d-PGJ2), and the downstream targets of PPARγ activity, adiponectin and resistin.

Methods

Single-center, prospective case–control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock.

Results

PPARγ nuclear protein expression was decreased but PPARγ activity was increased in PBMC from children with septic shock compared with controls. PPARγ activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) ± standard error of the mean (SEM) 0.03 versus 0.12 OD ± 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARγ ligand, 15d-PGJ2, compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 ± 21.7 versus 58 ± 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585–833 ng/ml versus 143 ng/ml, IQR 66–342 ng/ml; p < 0.05].

Conclusions

Sepsis is associated with altered PPARγ expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARγ in sepsis.
Appendix
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Metadata
Title
Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock
Authors
Jennifer M. Kaplan
Alvin Denenberg
Marie Monaco
Marchele Nowell
Hector Wong
Basilia Zingarelli
Publication date
01-01-2010
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 1/2010
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-009-1654-6

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