rhIL-1Ra reduces hepatocellular apoptosis in mice with acetaminophen-induced acute liver failure

Laboratory Investigation; a Journal of Technical Methods and Pathology
Jianjun HuYan Yu

Abstract

Acute liver failure (ALF) is a life-threatening disease that has proven difficult to cure. In Western countries, acetaminophen (APAP) poisoning is the most common cause of ALF. However, the mode of cell death in APAP-induced ALF cases is controversial. Previous studies have shown that administration of anti-interleukin-1 (anti-IL-1) antibody attenuated APAP-induced liver injury, and that administration of anti-IL-1 receptor antagonist (anti-IL-1Ra) antibody exacerbated organ injury. These results prompted us to investigate the roles of IL-1Ra in APAP-induced ALF mice. Our results show that administration of recombinant human IL-1Ra (rhIL-1Ra) could significantly improve the survival rate of mice with ALF induced by APAP. Furthermore, we found that rhIL-1Ras could dramatically inhibit the activities of alanine aminotransferase and aspartate aminotransferase in serum, reduce the death of hepatocytes and accelerate the proliferation of hepatocytes. In addition, we show that hepatocellular apoptosis rather than necrosis was the major cause of ALF-induced animal death, and that the anti-apoptosis role of rhIL-1Ra was mediated by reducing the release of cytochrome c from the mitochondria, and the activities of caspase-3, caspase-8 an...Continue Reading

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Apr 10, 2013·World Journal of Gastroenterology : WJG·Xiao-Lei ShiYi-Tao Ding
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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis