胆红素
医学
丸(消化)
炎症
药理学
胆绿素
脂多糖
内科学
灌注
内分泌学
免疫学
化学
血红素
生物化学
血红素加氧酶
酶
作者
Alexandra Kadl,Jens Pontiller,Markus Exner,Norbert Leitinger
出处
期刊:Shock
[Ovid Technologies (Wolters Kluwer)]
日期:2007-11-01
卷期号:28 (5): 582-588
被引量:51
标识
DOI:10.1097/shk.0b013e31804d41dd
摘要
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.
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