Non-alcoholic steatohepatitis weakens the acute phase response to endotoxin in rats

Thomsen, Karen L., Hebbard, Lionel, Glavind, Emilie, Clouston, Andrew, Vilstrup, Hendrik, George, Jacob and Gronbaek, Henning (2014) Non-alcoholic steatohepatitis weakens the acute phase response to endotoxin in rats. Liver International, 34 10: 1584-1592. doi:10.1111/liv.12547

Author Thomsen, Karen L.
Hebbard, Lionel
Glavind, Emilie
Clouston, Andrew
Vilstrup, Hendrik
George, Jacob
Gronbaek, Henning
Title Non-alcoholic steatohepatitis weakens the acute phase response to endotoxin in rats
Journal name Liver International   Check publisher's open access policy
ISSN 1478-3223
Publication date 2014-11-01
Year available 2014
Sub-type Article (original research)
DOI 10.1111/liv.12547
Open Access Status Not Open Access
Volume 34
Issue 10
Start page 1584
End page 1592
Total pages 9
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Background & Aims: Patients with non-alcoholic steatohepatitis (NASH) have increased mortality, including from infections. We, therefore, tested in a rodent model of steatohepatitis whether the hepatic acute phase response is intact.

Methods: Steatohepatitis was induced in rats by feeding a high-fat, high-cholesterol diet for 4 (early) and 16 weeks (advanced NASH). 2 h after low-dose LPS (0.5 mg/kg i.p.), we measured the serum concentrations of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We also measured liver mRNA's and the serum concentrations of acute phase proteins 24 h after LPS.

Results: Non-alcoholic steatohepatitis in itself increased the liver mRNA levels of TNF-α and IL-6 and also the liver mRNA and serum levels of the acute phase proteins. The exposure to LPS increased serum TNF-α in both early and advanced NASH and more so than in the control rats. However, the increases in acute phase protein genes in liver tissue and proteins in the blood were lower than in the control rats.

Conclusion: In rats with early or advanced experimental NASH, LPS despite an increased interleukin release resulted in a blunted acute phase protein response. This tachyphylaxis may be part of the mechanism for the increased infection susceptibility of patients with NASH. We speculate that the steatosis-related interleukin release desensitises the signalling pathway leading to acute phase protein synthesis.
Keyword Acute phase response
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 632630
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
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