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

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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.

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Acknowledgments

We would like to thank the parents who enrolled their children into this study during an emotionally difficult time. Supported, in part, by grants K12 HD028827 (J.M.K.), T32 ES10957 (J.M.K.), R01 GM067202 (B.Z.), and R01 GM064619 (H.W.) from the NIH, Bethesda, MD, and by the Translational Research Initiative at Cincinnati Children’s Hospital Medical Center (J.M.K.).

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Authors and Affiliations

  1. Cincinnati Children’s Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 2005, Cincinnati, OH, 45229-3039, USA

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

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  1. Jennifer M. Kaplan
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  2. Alvin Denenberg
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  3. Marie Monaco
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Correspondence to Jennifer M. Kaplan.

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Kaplan, J.M., Denenberg, A., Monaco, M. et al. Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock. Intensive Care Med 36, 123–130 (2010). https://doi.org/10.1007/s00134-009-1654-6

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  • DOI: https://doi.org/10.1007/s00134-009-1654-6

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