title: Kinin B1 Receptor Inhibition With BI113823 Reduces Inflammatory Response, Mitigates Organ Injury, and Improves Survival Among Rats With Severe Sepsis.
abstract: 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 ĸB 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: Department of BIN Fusion Technology, World Class University Program, Chonbuk National University, Jeonju, Korea.
authors: Priya
authors: P
authors: Murugesan
authors: Respiratory Diseases Research, Boehringer Ingelheim Pharma, Biberach, Germany.
authors: Birgit
authors: B
authors: Jung
authors: Department of BIN Fusion Technology, World Class University Program, Chonbuk National University, Jeonju, Korea.
authors: Dongwon
authors: D
authors: Lee
authors: Department of BIN Fusion Technology, World Class University Program, Chonbuk National University, Jeonju, Korea.
authors: Gilson
authors: G
authors: Khang
authors: Respiratory Diseases Research, Boehringer Ingelheim Pharma, Biberach, Germany.
authors: Henri
authors: H
authors: Doods
authors: Department of BIN Fusion Technology, World Class University Program, Chonbuk National University, Jeonju, Korea Department of Research, Mount Sinai Medical Center, Miami Beach, Florida.
authors: Dongmei
authors: D
authors: Wu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D065169:Bradykinin B1 Receptor Antagonists / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007249:Inflammation / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D017208:Rats, Wistar; D018805:Sepsis / Q000188:drug therapy* / Q000473:pathology*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D065169:Bradykinin B1 Receptor Antagonists
keywords: Kinin B1 receptor; multiorgan injury; proinflammatory mediator; sepsis