Innate Immunity and Inflammation in Sepsis in a Mouse Model for Binge Drinking
Jan, Basit Latief
AdvisorPruett, Stephen B.
CommitteePharr, G. Todd
Alcohol consumption is a significant risk-factor for mortality in patients with sepsis. This study was carried to investigate the mechanisms by which acute ethanol exposure alters the course of sepsis and the effect of TLR4 signaling. Ethanol administration decreases resistance to E. coli and causes decrease in the ability to clear bacteria both from the peritoneal-cavity as well as the spleen. At early time-points, ethanol also suppresses the production of pro-inflammatory cytokines. TLR4 is dispensable for survival in E. coli sepsis but it also contributes to lethality in wild-type mice. Although TLRs have been implicated as an important element of host defense against infections, evidence indicates that these receptors may also play a crucial role in the pathophysiology of sepsis.