Protective effect of recombinant human IL-1Ra on CCl4-induced acute liver injury in mice.
World J Gastroenterol
; 16(22): 2771-9, 2010 Jun 14.
Article
in En
| MEDLINE
| ID: mdl-20533597
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 (CCl(4)).METHODS:
Acute liver damage was induced by injecting 8-wk-old mice with CCl(4) 1 mL/kg (13 dilution in corn oil) intraperitoneally (ip). Survival after liver failure was assessed by injecting 8-wk-old mice with a lethal dose of CCl(4) 2.6 mL/kg (11 dilution in corn oil) ip. Mice were subcutaneously injected with 1 mg/kg recombinant human IL-1Ra twice a day after CCl(4) treatment for 5 d. Serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) levels were determined with a commercial assay kit. Serum IL-1beta, IL-1Ra levels were measured by enzyme-linked immunosorbent assay kit. Quantitative real-time polymerase chain reaction was used to determine liver IL-1beta, IL-1Ra and IL-6 expression during CCl(4)-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 CCl(4)-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombinant Proteins
/
Carbon Tetrachloride
/
Cytoprotection
/
Interleukin 1 Receptor Antagonist Protein
/
Liver
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
World J Gastroenterol
Journal subject:
GASTROENTEROLOGIA
Year:
2010
Document type:
Article
Affiliation country:
China