The treatment with a ligand of Transcriptional Factor improves sepsis survival through anti-inflammatory effects

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Objective: Septic shock is the most common cause of death in intensive care unit next to cardiovascular diseases. Unfortunately, no effective treatment for this condition currently exists. Peroxisome proliferator-activated receptor (PPAR)-_Yligands are reported to reduce inflammatory responses. To evaluate the hypothesis that PPAR-_Yligands improve survival of septic shock, a mouse model of sepsis (apolipoprotein E (ApoE) knockout) was used and treated with pioglitazone, a PPAR-_Yligand. ApoE knockout mice have high mortality rate in sepsis due to lack of endotoxin clearance. Design and settings; Prospective laboratory study in a university laboratory. Subjects: Total 72 male ApoE knock out mice and 60 wild type C57/B6 mice randomized into three groups (sepsis, pre-treatment, post-treatment). Interventions; Cecal ligation and puncture were done in the sepsis and treatment groups. Mice injected with pioglitazone (5mg/kg/day) on the day before operation or mice injected with pioglitazone 6 hours after operation. Measurements and Main Results: Both pre- and post- operation treatment of pioglitazone improved survival of mortality in ApoE knock out and wild type mice. Serum levels of cytokines and chemokines, myeloperoxidase activity of lung and liver showed the same suppression in pioglitazone treatment group. Pioglitazone also suppressed monocytes adhesion to vascular endothelium under flow condition. Conclusions: Pioglitazone improved survival rate of apoE knockout mice after onset of septic shock through suppression of inflammatory respon