Original Article
Copyright ©2010 Baishideng. All rights reserved.
World J Gastroenterol. Jun 14, 2010; 16(22): 2771-2779
Published online Jun 14, 2010. doi: 10.3748/wjg.v16.i22.2771
Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice
Run-Zhi Zhu, Di Xiang, Chao Xie, Jing-Jing Li, Jian-Jun Hu, Hong-Lin He, Yun-Sheng Yuan, Jin Gao, Wei Han, Yan Yu
Run-Zhi Zhu, Chao Xie, Jing-Jing Li, Hong-Lin He, Yun-Sheng Yuan, Yan Yu, Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China
Di Xiang, Jin Gao, Wei Han, Laboratory of Regeneration, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
Chao Xie, Department of Food Science, Stocking Hall, Cornell University, Ithaca, NY 14853-7201, United States
Jian-Jun Hu, Department of Infectious Disease, Shanghai No. 6 People’s Hospital, College of Medicine, Shanghai Jiao Tong University, Shanghai 200233, China
Author contributions: Zhu RZ, Xiang D, Xie C, Li JJ, Hu JJ, He HL, Yuan YS and Gao J performed the majority of experiments and data analysis; Han W and Yu Y designed the study and wrote the manuscript.
Supported by The Chinese Human Liver Proteome Project, No. 2004BA711A19-08 and National 863 Project, No. 2007AA02Z100
Correspondence to: Yan Yu, PhD, Shanghai Municipality Key Laboratory of Veterinary Biotechnology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China. yanyu@sjtu.edu.cn
Telephone: +86-21-34205769 Fax: +86-21-34205833
Received: March 14, 2010
Revised: April 15, 2010
Accepted: April 22, 2010
Published online: June 14, 2010
Abstract

AIM: To evaluate the effects of positive regulation of recombinant human interleukin 1 receptor antagonist (rhIL-1Ra) on hepatic tissue recovery in acute liver injury in mice induced by carbon tetrachloride (CCl4).

METHODS: Acute liver damage was induced by injecting 8-wk-old mice with CCl4 1 mL/kg (1:3 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl4 2.6 mL/kg (1:1 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl4 treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1β, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1β, IL-1Ra and IL-6 expression during CCl4-induced acute liver injury. Liver sections were stained with hematoxylin-eosin. A histology-injury grading system was used to evaluate the degree of necrosis after acute liver injury. Proliferating cell nuclear antigen (PCNA) staining was used to evaluate the role of rhIL-1Ra in promoting hepatocyte proliferation.

RESULTS: Quantitative analysis showed a higher level of IL-6 mRNA expression and reduced serum AST and ALT levels in the livers of the rhIL-1Ra-treated group at the early phase of CCl4-induced acute liver injury. Histological examination indicated a decrease in centrilobular necrotic areas in mice treated with rhIL-1Ra, and a novel role of rhIL-1Ra in promoting hepatocyte proliferation was also supported by an increase of PCNA staining. All these results, accompanied by a strong survival benefit in rhIL-1Ra-treated vs PBS-treated groups, demonstrated that rhIL-1Ra administration ameliorated the histological damage and accelerated the regeneration and recovery process of the liver.

CONCLUSION: rhIL-1Ra could be further developed as a novel therapeutic agent for the treatment of acute liver injury because of its ability to reduce hepatocellular damage and facilitate liver regeneration.

Keywords: Recombinant human interleukin 1 receptor antagonist; Carbon tetrachloride; Liver injury; Hepatocyte proliferation