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.