Adiponectin Deficiency Promotes the Production of Inflammatory Mediators While Severely Exacerbating Hepatic Injury in Mice with Polymicrobial Sepsis

作者：Uji Yoshitaka; Yamamoto Hiroshi^*; Maeda Kazuhisa; Tsuchihashi Hiroshi; Akabori Hiroya; Shimizu Tomoharu; Endo Yoshihiro; Shimomura Iichiro; Tani Tohru

来源：Journal of Surgical Research, 2010, 161(2): 301-311.

DOI：10.1016/j.jss.2008.12.021

• adiponectin
• sepsis
• monocyte chemoattractant protein-1
• hepatic injury
• peroxisome proliferator-activated receptor gamma

Background. Adiponectin (APN), which is an adipose tissue-derived hormone, is known as an anti-inflammatory cytokine. The effects of APN on the production of inflammatory mediators and hepatic injury during polymicrobial sepsis were evaluated using APN-knockout (KO) mice that had undergone a cecal ligation and puncture (CLP) and rosiglitazone, a selective peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, which increases the plasma APN concentration.
Materials and Methods. Wild type (WT) and APN-KO mice were underwent CLP. The plasma and hepatic levels of inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1), were measured before, at 24, and 48 h after CLP. A histological analysis of the liver and the plasma alanine aminotransferase (ALT) levels were examined to evaluate hepatic injury. The plasma levels of inflammatory mediators after CLP with pretreatment of rosiglitazone were compared with those without rosiglitazone.
Results. APN deficiency resulted in significant increases in the plasma levels of TNF-a, IL-6, and MCP-1 at 24 h after CLP. Hepatic MCP-1 and plasma AST levels in APN-KO mice were significantly higher than those in WT mice at 48 h after CLP. A steatosis change and MCP-1 expressions in hepatocytes were induced in APN-KO mice during sepsis. The administration of rosiglitazone significantly lowered the plasma levels of inflammatory mediators, including TNF-a, IL-6, and MCP-1, in WT mice but not in APN-KO mice during sepsis.
Conclusion. These results suggest that an APN deficiency induces an excessive systemic inflammatory status and exacerbates hepatic injury during polymicrobial sepsis.

• 出版日期2010-6-15