Peroxisome proliferator-activated receptor γ-induced T cell apoptosis reduces survival during polymicrobial sepsis.

Rationale: Despite intensive research, sepsis displays the most prevalent cause of death on intensive care units. The hallmark of sepsis is an overshooting T-cell death that reduces host defense mechanisms and that is associated with poor patient survival. Previous in vitro studies revealed that the expression of the transcription factor peroxisome proliferator–activated receptor (PPAR) γ was increased in isolated T cells of patients with sepsis.Objectives: We determined the importance of targeting PPARγ for sepsis treatment and underlying molecular mechanisms for T-cell apoptosis in vivo.Methods: To mimic human systemic inflammation and septic conditions, we used a nonlethal endotoxemia and a lethal cecum ligation and puncture polymicrobial sepsis model.Measurements and Main Results: PPARγ inhibition in T cells with either the PPARγ antagonist GW9662 or a newly generated T cell–specific PPARγ knockout (Tc-PPARγ−/−) mice provided a survival advantage during polymicrobial sepsis in mice, which correlated w...