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

Jennifer M Kaplan1, Alvin Denenberg, Marie Monaco

  • 1Cincinnati 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

Intensive Care Medicine
|September 18, 2009
PubMed

Insights

Sepsis alters peroxisome proliferator-activated receptor-gamma (PPARgamma) in critically ill children, affecting its activity and downstream targets like adipokines. These adipokines may serve as biomarkers for sepsis severity and outcomes.

Area of Science:

  • Molecular biology
  • Pediatric critical care
  • Endocrinology

Background:

  • Sepsis is a life-threatening condition in children characterized by a dysregulated host response to infection.
  • Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor involved in inflammation and metabolism.
  • Understanding molecular changes in sepsis is crucial for identifying new therapeutic targets.

Purpose of the Study:

  • To evaluate changes in PPARgamma expression and activity in peripheral blood mononuclear cells (PBMC) of critically ill children with sepsis.
  • To investigate the impact of sepsis on the PPARgamma ligand 15-deoxy-(12,14)-PGJ(2) (15d-PGJ(2)).
  • To assess the levels of PPARgamma downstream targets, adiponectin and resistin, in pediatric sepsis.

Main Methods:

  • A prospective case-control study was conducted in a single center.
  • Involved critically ill children diagnosed with systemic inflammatory response syndrome, sepsis, or septic shock.
  • Measured PPARgamma protein expression, activity, 15d-PGJ(2) levels, and plasma adipokines (adiponectin, resistin).

Main Results:

  • PPARgamma activity was increased in PBMC of children with septic shock, despite decreased nuclear protein expression.
  • PPARgamma activity correlated positively with the Pediatric Risk of Mortality (PRISM) score.
  • Increased levels of 15d-PGJ(2), adiponectin, and resistin were observed in sepsis patients, with resistin levels higher in non-survivors.

Conclusions:

  • Sepsis significantly alters PPARgamma expression and activity in pediatric patients.
  • Plasma adipokines (adiponectin and resistin) show correlation with sepsis severity scores and mortality.
  • Further research is warranted to elucidate the mechanisms of PPARgamma dysregulation in sepsis.
Abstract

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