Pioglitazone reduces systematic inflammation and improves mortality in apolipoprotein E knockout mice with sepsis
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- Haraguchi, G., Kosuge, H., Maejima, Y. et al. Intensive Care Med (2008) 34: 1304. doi:10.1007/s00134-008-1024-9
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To determine whether peroxisome proliferator-activated receptor (PPAR) γ ligands improve survival of patients with septic shock we treated a mouse model of sepsis [apolipoprotein (Apo) E) knockout mice] with pioglitazone, a PPAR-γ ligand. ApoE knockout mice have a high mortality rate due to sepsis because the endotoxin is not cleared.
Design and setting
Prospective study in a university laboratory.
We assorted 87 male ApoE knockout mice and 60 wild-type C57/B6 mice randomly into three groups (sepsis, pretreatment, posttreatment).
Cecal ligation and puncture (CLP) was carried out in the sepsis and treatment groups. Mice were injected with pioglitazone (5 mg/kg per day) on the day before CLP or 6 h after surgery.
Measurements and results
Both pre- and post-CLP treatment with pioglitazone improved survival of ApoE knockout and wild-type mice. Serum levels of cytokines and chemokines and myeloperoxidase activity in lung and liver were suppressed in the pioglitazone-treated group. Pioglitazone also suppressed monocyte adhesion to vascular endothelium under flow conditions.
Pioglitazone improved survival of ApoE knockout mice after onset of septic shock through suppression of inflammatory responses.