Decreased inflammatory status has been reported in subjects with mild unconjugated hyperbilirubinemia. However, mechanisms of the anti-inflammatory actions of bilirubin (BR) are not fully understood. The aim of this study is to assess the role of BR in systemic inflammation using hyperbilirubinemic Gunn rats as well as their normobilirubinemic littermates and further in primary hepatocytes. The rats were treated with lipopolysaccharide (LPS, 6 mg/kg intraperitoneally) for 12 h, their blood and liver were collected for analyses of inflammatory and hepatic injury markers. Primary hepatocytes were treated with BR and TNF-α. LPS-treated Gunn rats had a significantly decreased inflammatory response, as evidenced by the anti-inflammatory profile of white blood cell subsets, and lower hepatic and systemic expressions of IL-6, TNF-α, IL-1β, and IL-10. Hepatic mRNA expression of LPS-binding protein was upregulated in Gunn rats before and after LPS treatment. In addition, liver injury markers were lower in Gunn rats as compared to in LPS-treated controls. The exposure of primary hepatocytes to TNF-α with BR led to a milder decrease in phosphorylation of the NF-κB p65 subunit compared to in cells without BR. In conclusion, hyperbilirubinemia in Gunn rats is associated with an attenuated systemic inflammatory response and decreased liver damage upon exposure to LPS.

• Keywords
• Gunn rats, LPS, NF-κB, bilirubin, hyperbilirubinemia, inflammation,
• MeSH
• Apoptosis drug effects   MeSH
• Bilirubin pharmacology   MeSH
• Biomarkers blood   MeSH
• Cytokines blood   genetics   metabolism   MeSH
• Cytoprotection drug effects   MeSH
• Phosphorylation drug effects   MeSH
• Hepatocytes metabolism   MeSH
• Hyperbilirubinemia blood   complications   MeSH
• Liver metabolism   MeSH
• Cells, Cultured MeSH
• Leukocytes metabolism   MeSH
• Lipopolysaccharides MeSH
• RNA, Messenger genetics   metabolism   MeSH
• NF-kappa B metabolism   MeSH
• Rats, Gunn MeSH
• Signal Transduction MeSH
• Inflammation complications   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bilirubin MeSH
• Biomarkers MeSH
• Cytokines MeSH
• Lipopolysaccharides MeSH
• RNA, Messenger MeSH
• NF-kappa B MeSH

The strong effects of bilirubin on various levels of the immune system are multifactorial. Concerning the mechanisms of these effects, we hypothesize that the primary causes of the described actions of bilirubin are the direct interaction of bilirubin molecules with cell membranes.

• MeSH
• Bilirubin immunology   pharmacology   MeSH
• Immunosuppressive Agents pharmacology   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Bilirubin MeSH
• Immunosuppressive Agents MeSH

The effect of an i.p. application of bilirubin on phagocytic activity and the arrangement of the microtubule system of murine peritoneal macrophages were examined. A significant increase of phagocytic activity was observed 3 h after bilirubin treatment, and normal value were reached after 3 d. The increase of the extent of the microtubule system was comparable with that of enhanced phagocytosis but normal values were observed after 1 d.

• MeSH
• Bilirubin pharmacology   MeSH
• Phagocytosis drug effects   MeSH
• Macrophages drug effects   physiology   MeSH
• Microtubules drug effects   metabolism   physiology   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Peritoneal Cavity cytology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bilirubin MeSH