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

作     者：LU Zhong-qiu LI Meng-fang QIU Qiao-meng LIANG Huang ZHOU Tie-li HONG Guang-liang WU Bin 

作者机构：Department of Emergency First Affiliated Hospital of Wenzhou Medical College. Wenzhou Zhejiang 325000 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2009年第122卷第16期

页      面：1910-1916页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：Zhejiang Medical Key Assistance Programme [07-1704] Zhejiang Technology Project [2005C30009] Key Project of Wenzhou Technology Bureau [Y2004A004] 

主　　题：Vibrio vulnificus sepsis toll-like receptors inflammatory cytokines cefoperazone sodium levofloxacin 

摘      要：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-α （TNF-α）, interleukin （IL）-1β, 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-α, IL-1β and IL-6 were significantly elevated in group AV as a function of infection. In group AVA as compared to AV, expression of TNF-α and IL-1β 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.