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

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),antimicrob;al-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-β 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.