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The Anti-Inflammatory Role of Bilirubin on "Two-Hit" Sepsis Animal Model.

AbstractINTRODUCTION:
Bilirubin is a product of the heme catabolism pathway, and it is excreted in bile and removed from the body through the urine. Bilirubin has potent antioxidant properties but also plays a role in anti-inflammation by protecting the body against endotoxin-induced lung inflammation, down-regulating the expression of adhesion molecules, and inhibiting the infiltration of inflammatory cells. Thus, bilirubin is a promising agent that could use in inflammation disease treatment. The application of bilirubin on the "two-hit" sepsis animal model has been, to date, unknown.
METHODS:
we used lipopolysaccharide to induce initial insults in C57BL/6 mice. After 24 h, mice underwent cecal ligation and puncture to induce the "two-hit" sepsis model. Next, mice were administered 30 mg/kg bilirubin and we observed an improvement.
RESULTS:
We observed that bilirubin inhibited the expression of pro-inflammatory cytokines, while the levels of anti-inflammatory cytokines were significantly augmented in the lung. Bilirubin improved the survival rate in the sepsis model. Furthermore, we suggest that bilirubin can modulate the accumulation of T-regulatory cells and myeloid-derived suppressor cells. Notably, bilirubin suppressed the activation and functions of T-cells.
CONCLUSIONS:
These results clarified that bilirubin might improve tissue injury in sepsis through anti-inflammatory mechanisms.
AuthorsDuc Tin Tran, Yong Yeon Jeong, Jeong Min Kim, Hong Bum Bae, Sung Kuk Son, Sang Hyun Kwak
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 22 (Nov 17 2020) ISSN: 1422-0067 [Electronic] Switzerland
PMID33212789 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents
  • Bilirubin
Topics
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Bilirubin (pharmacology)
  • Disease Models, Animal
  • Lymphocyte Activation (drug effects)
  • Male
  • Mice
  • Myeloid-Derived Suppressor Cells (immunology, pathology)
  • Sepsis (drug therapy, immunology, pathology)
  • T-Lymphocytes, Regulatory (immunology, pathology)

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