Pretreatment with troglitazone decreases lethality during endotoxemia in mice

Karen Reynolds, Bo Novosad, Adam Hoffhines, Jenny Gipson, Jared Johnson, Jeffrey Peters, Frank Gonzalez, Jeffrey Gimble, Molly Hill

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Troglitazone is an oral antidiabetic drug that is a ligand for peroxisome proliferator activated receptor γ (PPARγ). Based on other studies that have implicated an immunosuppressive role for PPARγ during inflammatory responses, we hypothesized that troglitazone treatment would improve survival in a murine model of endotoxemia and that the protective effect would be mediated by decreased expression of inflammatory mediators. C57B1/6N x Sv/129 (wild-type [WT]) or PPARα null mice treated for 2 weeks with dietary troglitazone (0.1%) had significantly fewer deaths and a higher LD50 value compared to control-fed mice when challenged with lipopolysaccharide (LPS). PPARα null mice were more sensitive to the lethal effects of LPS as evidenced by a 2-fold lower LD50 (6.6 mg/kg) compared to WT mice (14.6 mg/kg). Troglitazone treatment had no significant effect on LPS-induced plasma TNF, glucose, or nitric oxide levels in WT or PPARα null mice at any of the time points examined. However, troglitazone treatment significantly reduced LPS-induced plasma IL-6 levels in both WT and PPARα null mice. The results of these studies suggest that troglitazone treatment protects mice against a lethal challenge of LPS, but whether or not this effect is mediated through decreased expression of inflammatory mediators remains unclear.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalJournal of Endotoxin Research
Volume8
Issue number4
DOIs
StatePublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Molecular Biology
  • Cell Biology
  • Infectious Diseases

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