Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 213, Issue 4, Pages 532-540Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv426
Keywords
Kinin B1 receptor; proinflammatory mediator; multiorgan injury; sepsis
Categories
Funding
- Boehringer Ingelheim Pharma
- Brain Korea 21 PLUS Project, National Research Foundation of Korea (NRF)
- Korean Ministry of Education, Science and Technology [2012007331]
Ask authors/readers for more resources
Background. This study examined the therapeutic effects of an orally active nonpeptide kinin B1 receptor antagonist, BI113823, in a clinically relevant experimental model of polymicrobial sepsis in rats. Methods. Sepsis was induced by cecal ligation and puncture (CLP). Animals received treatment with either vehicle or BI113823. The experiment was terminated in the first set of animals 15 hours after CLP. Seven-day survival following CLP was determined in the second set of animals. Results. Compared with vehicle treatment, administration of BI113823 reduced neutrophil and macrophage infiltration, reduced cytokine production, attenuated intestinal mucosal hyperpermeability, prevented hemodynamic derangement, and improved cardiac output. Furthermore, administration of BI113823 reduced inducible nitric oxide synthase expression and the injury score in the lung and attenuated nuclear factor kappa B activation and apoptosis in the liver. Treatment with BI113823 also reduced plasma levels of cardiac troponin, aspartate aminotransferase, alanine aminotransferase, urea, and lactate, as well as proteinuria. Finally, administration of BI113823 improved the 7-day survival rate following CLP in rats. Conclusions. Administration of BI113823 reduced systemic and tissue inflammatory responses, prevented hemodynamic derangement, attenuated multiorgan injury, and improved overall survival.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available