Pioglitazone reduces systematic inflammation and improves mortality in apolipoprotein E knockout mice with sepsis.

Abstract

OBJECTIVE:

To determine whether peroxisome proliferator-activated receptor (PPAR) gamma ligands improve survival of patients with septic shock we treated a mouse model of sepsis [apolipoprotein (Apo) E) knockout mice] with pioglitazone, a PPAR-gamma 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.

SUBJECTS:

We assorted 87 male ApoE knockout mice and 60 wild-type C57/B6 mice randomly into three groups (sepsis, pretreatment, posttreatment).

INTERVENTIONS:

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.

CONCLUSIONS:

Pioglitazone improved survival of ApoE knockout mice after onset of septic shock through suppression of inflammatory responses.

• Authors: Go Haraguchi, Hisanori Kosuge, Yasuhiro Maejima, Jun-Ichi Suzuki, Takasuke Imai, Masayuki Yoshida, Mitsuaki Isobe
• Journal: Intensive care medicine (Intensive Care Med) Vol. 34 Issue 7 Pg. 1304-12 (Jul 2008) ISSN: 0342-4642 [Print] United States
• PMID: 18283431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Cytokines
• Hypoglycemic Agents
• Thiazolidinediones
• Peroxidase
• Pioglitazone

Topics

• Animals
• Apolipoproteins E (blood)
• Cytokines (blood)
• Enzyme-Linked Immunosorbent Assay
• Hypoglycemic Agents (therapeutic use)
• Inflammation (drug therapy)
• Liver (drug effects, enzymology, pathology)
• Lung (drug effects, enzymology, pathology)
• Male
• Mice
• Mice, Knockout
• Peroxidase (metabolism)
• Pioglitazone
• Sepsis (drug therapy, metabolism, mortality)
• Thiazolidinediones (therapeutic use)