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.
BACKGROUND
Septicemia 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.


METHODS
Male 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.


RESULTS
mRNAs 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.


CONCLUSIONS
Antimicrobial 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.
Department of Emergency, First Affiliated Hospital of Wenzhou Medical College, Zhejiang, China. lzq640815@163.com
Zhong-qiu
ZQ
Lu
Meng-fang
MF
Li
Qiao-meng
QM
Qiu
Huang
H
Liang
Tie-li
TL
Zhou
Guang-liang
GL
Hong
Bin
B
Wu
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000188:drug therapy* / Q000235:genetics / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014735:Vibrio Infections / Q000188:drug therapy; D041261:Vibrio vulnificus / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D000890:Anti-Infective Agents; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10