Interleukin-6 inhibits oxidative injury and necrosis after extreme liver resection

Xiaoling Jin, Zongxiu Zhang, Donna Beer-Stolz, Teresa A. Zimmers, Leonidas G. Koniaris

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Extreme hepatectomy or resection of more than 80% of liver mass often leads to liver failure and death and is a major limitation to therapeutic liver resection for patients with liver tumors. We sought to define the mechanisms leading to liver failure and to determine the utility of interleukin-6 (IL-6) administration to improve outcomes. Mice were injected with Chinese hamster ovary cells expressing human IL-6 or no recombinant protein, or were administered recombinant IL-6 or carrier by osmotic mini-pump. Mice were then subjected to 70% or 87% hepatectomy. Light and electron microscopy of liver sections after 87% hepatectomy showed ballooning hepatocytes, vacuolar changes, and mitochondrial abruption, with absence of anoikic nuclei. No significant activation of executor caspases or DNA laddering was observed, although a dramatic decrease in cellular adenosine triphosphate (ATP) stores was measured, suggesting cell death was by a necrotic pathway involving mitochondrial dysfunction. A large increase in protein oxidation was observed, indicative of significant oxidative stress. IL-6 treatment before 87% hepatectomy resulted in less biochemical and histological evidence of liver injury as well as earlier proliferating chain nuclear antigen (PCNA) expression and accelerated recovery of liver mass. IL-6 pretreatment induced the antioxidative injury proteins, ref-1 and GPX1, decreased protein oxidation, vacuolar changes and leakage of mitochondrial products, improved ATP stores, and maintained cellular ultrastructure after 87% hepatectomy. Conclusion: Massive oxidative injury and mitochondrial dysfunction occurs in the liver after extreme hepatectomy. IL-6 improves recovery and survival from extreme liver resection by enhancing pro-growth pathways, reducing oxidative stress, and maintaining mitochondrial function.

Original languageEnglish (US)
Pages (from-to)802-812
Number of pages11
JournalHepatology
Volume46
Issue number3
DOIs
StatePublished - Sep 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Interleukin-6 inhibits oxidative injury and necrosis after extreme liver resection'. Together they form a unique fingerprint.

  • Cite this