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

• Published in: International journal of molecular sciences 2020-11, Vol.21 (22), p.8650
• Main Authors: Tran, Duc Tin, Jeong, Yong Yeon, Kim, Jeong Min, Bae, Hong Bum, Son, Sung Kuk, Kwak, Sang Hyun
• Format: Article
• Language: English
• Subjects: Animal models; Animals; anti-inflammation; Anti-Inflammatory Agents - pharmacology; Antioxidants; Bile; Bilirubin; Bilirubin - pharmacology; Catabolism; cecal ligation and puncture; Cecum; Cell adhesion molecules; Cytokines; Disease Models, Animal; Endotoxins; Failure; Heme; Immunoregulation; Infections; Inflammation; lipopolysaccharide; Lipopolysaccharides; Lungs; Lymphocyte Activation - drug effects; Lymphocytes T; Male; Medical research; Mice; Mortality; Myeloid-Derived Suppressor Cells - immunology; Myeloid-Derived Suppressor Cells - pathology; Oxidative stress; Sepsis; Sepsis - drug therapy; Sepsis - immunology; Sepsis - pathology; Suppressor cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology; Tumor necrosis factor-TNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228650

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. 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. 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. These results clarified that bilirubin might improve tissue injury in sepsis through anti-inflammatory mechanisms.