Single bolus injection of bilirubin improves the clinical outcome in a mouse model of endotoxemia.

Abstract

Increasing serum levels of biliverdin and bilirubin was shown to be beneficial in settings of inflammation. Bilirubin was shown to be protective in LPS-induced lung injury in rats; however, the exact mechanism remains elusive. Here, we investigated whether a single bolus injection of bilirubin would exert anti-inflammatory effects in a mouse model of endotoxemia. Mice were challenged with sublethal doses (2 mg/kg body weight) of LPS, and the effects of intravenously administered bilirubin (40 mg/kg body weight) were assessed. In contrast to control animals, bilirubin-treated animals fully recovered from endotoxin shock within 24 h. Bilirubin treatment improved the clinical score significantly at all time points assessed, attenuated weight loss, and improved LPS-induced anorexia. Furthermore, bilirubin treatment inhibited LPS-induced leukocyte-endothelial interactions and leukocyte accumulation in various tissues. Expression of inflammatory genes, including endothelial adhesion molecules, but also IL-1beta and TNF-alpha, was significantly reduced in bilirubin-treated animals. Moreover, bilirubin inhibited LPS-induced expression of inflammatory genes in isolated cultured aortic endothelial cells and in bone marrow-derived macrophages. These data show that single-dose administration of bilirubin attenuates tissue injury induced by endotoxin, and that bilirubin, in addition to its antioxidant effects, also exerts potent anti-inflammatory activity.

• Authors: Alexandra Kadl, Jens Pontiller, Markus Exner, Norbert Leitinger
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 28 Issue 5 Pg. 582-8 (Nov 2007) ISSN: 1073-2322 [Print] United States
• PMID: 17577133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Cell Adhesion Molecules
• Inflammation Mediators
• Interleukin-1beta
• Lipopolysaccharides
• Tumor Necrosis Factor-alpha
• Biliverdine
• Bilirubin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Bilirubin (blood, pharmacology)
• Biliverdine (blood)
• Cell Adhesion Molecules (biosynthesis)
• Cell Communication (drug effects)
• Cells, Cultured
• Disease Models, Animal
• Endothelial Cells (metabolism, pathology)
• Endotoxemia (chemically induced, drug therapy, metabolism, pathology)
• Gene Expression Regulation (drug effects)
• Inflammation Mediators (metabolism)
• Interleukin-1beta (biosynthesis)
• Leukocytes (metabolism, pathology)
• Lipopolysaccharides (toxicity)
• Lung (metabolism, pathology)
• Lung Injury
• Macrophages (metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Rats
• Time Factors
• Tumor Necrosis Factor-alpha (biosynthesis)