Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock.
OBJECTIVE
To assess changes in peroxisome proliferator-activated receptor-gamma (PPARgamma) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARgamma, 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)), and the downstream targets of PPARgamma 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
PPARgamma nuclear protein expression was decreased but PPARgamma activity was increased in PBMC from children with septic shock compared with controls. PPARgamma 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 PPARgamma ligand, 15d-PGJ(2), 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 PPARgamma 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 PPARgamma in sepsis.
Kaplan
Jennifer M
JM
Cincinnati Children's Hospital Medical Center, The University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 2005, Cincinnati, OH 45229-3039, USA. Jennifer.Kaplan@cchmc.org
Denenberg
Alvin
A
Monaco
Marie
M
Nowell
Marchele
M
Wong
Hector
H
Zingarelli
Basilia
B
D054392:Adipokines / Q000097:blood; D015992:Body Mass Index; D002648:Child; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D047495:PPAR gamma / Q000502:physiology*; D052243:Resistin / Q000097:blood; D012772:Shock, Septic / Q000503:physiopathology*; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism / Q000503:physiopathology
D054392:Adipokines; D016207:Cytokines; D047495:PPAR gamma; C499624:RETN protein, human; D052243:Resistin