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.

Abstract

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.

• Authors: Zhong-qiu Lu, Meng-fang Li, Qiao-meng Qiu, Huang Liang, Tie-li Zhou, Guang-liang Hong, Bin Wu
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 122 Issue 16 Pg. 1910-6 (Aug 20 2009) ISSN: 2542-5641 [Electronic] China
• PMID: 19781370 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adaptor Proteins, Signal Transducing
• Anti-Infective Agents
• Cytokines
• Interleukin-1beta
• Interleukin-6
• Toll-Like Receptor 2
• Toll-Like Receptor 4
• Toll-Like Receptors
• Tumor Necrosis Factor-alpha
• Interleukin-10

Topics

• 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)