Effect of antimicrobial agents on the toll-like receptors and inflammatory cytokines in liver tissue of the alcohol-induced liver disease in rats with Vibrio vulnificus sepsis.
- Author:
Zhong-qiu LU
1
;
Meng-fang LI
;
Qiao-meng QIU
;
Huang LIANG
;
Tie-li ZHOU
;
Guang-liang HONG
;
Bin WU
Author Information
- Publication Type:Journal Article
- MeSH: Adaptor Proteins, Signal Transducing; genetics; Animals; Anti-Infective Agents; therapeutic use; Cytokines; genetics; Interleukin-10; genetics; Interleukin-1beta; genetics; Interleukin-6; genetics; Liver; drug effects; metabolism; Liver Diseases, Alcoholic; drug therapy; metabolism; Male; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Sepsis; drug therapy; genetics; microbiology; Toll-Like Receptor 2; genetics; Toll-Like Receptor 4; genetics; Toll-Like Receptors; genetics; Tumor Necrosis Factor-alpha; genetics; Vibrio Infections; drug therapy; Vibrio vulnificus; physiology
- From: Chinese Medical Journal 2009;122(16):1910-1916
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDSepticemia and inflammation-mediated septic shock caused by Vibrio vulnificus (VV) is strongly associated with chronic liver disease. This study examined the effects of antimicrobial therapy on expression of hepatic toll-like receptors and inflammatory cytokines in rats with alcohol-induced liver disease complicated by VV sepsis.
METHODSMale Sprague-Dawley rats were assigned to the following treatment groups: normal control (N), alcoholic liver disease control (A), antimicrobial-treated alcoholic liver disease control (AA), alcoholic liver disease with VV sepsis (AV), and antimicrobial-treated alcoholic liver disease with VV sepsis (AVA). Alcohol-induced liver disease was observed in all groups except N. Expression of mRNAs encoding hepatic toll-like receptors 2 and 4, myeloid differentiation protein-2, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6 and IL-10 was determined by RT-PCR.
RESULTSmRNAs encoding toll-like receptors 2 and 4 and myeloid differentiation protein-2 were significantly up-regulated in group AV as compared to control groups at 2 - 24 hours of sepsis; peak expression occurred at 12 hours. These mRNAs were also up-regulated in group AVA but to lesser degrees than in group AV at comparable time post-infection. mRNAs encoding TNF-alpha, IL-1beta and IL-6 were significantly elevated in group AV as a function of infection. In group AVA as compared to AV, expression of TNF-alpha and IL-1beta mRNAs was lower at 12 - 24 hours post-infection and expression of IL-6 mRNA was lower at 24 hours post-infection. Compared with control groups, IL-10 mRNA expression in group AV was markedly higher at 12 - 24 hours of sepsis. Expression of IL-10 mRNA was lower in group AVA as compared to AV at 24 hours of sepsis.
CONCLUSIONSAntimicrobial therapy reduces expression of toll-like receptors and cytokines in rats with alcohol-induced liver disease complicated by VV sepsis. Monitoring hepatic toll-like receptor and cytokine expression during antibiotic therapy may be valuable for determining the course of VV sepsis in subjects with liver disease.
