Reference - Detail
| RRC ID | 43276 |
|---|---|
| Author | Haraguchi G, Kosuge H, Maejima Y, Suzuki J, Imai T, Yoshida M, Isobe M. |
| Title | Pioglitazone reduces systematic inflammation and improves mortality in apolipoprotein E knockout mice with sepsis. |
| Journal | Intensive Care Med |
| 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. |
| Volume | 34(7) |
| Pages | 1304-12 |
| Published | 2008-7-1 |
| DOI | 10.1007/s00134-008-1024-9 |
| PMID | 18283431 |
| MeSH | Animals Apolipoproteins E / blood* Cytokines / blood Enzyme-Linked Immunosorbent Assay Hypoglycemic Agents / therapeutic use* Inflammation / drug therapy* Liver / drug effects* Liver / enzymology Liver / pathology Lung / drug effects* Lung / enzymology Lung / pathology Male Mice Mice, Knockout Peroxidase / metabolism Pioglitazone Sepsis / drug therapy* Sepsis / metabolism Sepsis / mortality Thiazolidinediones / therapeutic use* |
| IF | 17.679 |
| Times Cited | 25 |
| WOS Category | CRITICAL CARE MEDICINE |
| Resource | |
| Human and Animal Cells | THP-1(RCB1189) |