Binge alcohol consumption 18h after induction of sepsis in a mousemodel causes rapid overgrowth of bacteria, a cytokine storm,and decreased survival.

Abstract

Alcohol abuse increases vulnerability to infections and infection-related mortality. In previous studies, we found that acute alcohol abuse in a binge-drinking model in mice decreased resistance to bacterial sepsis when alcohol was administered near the time of bacterial challenge. In the present study, we investigated the effects of alcohol administered later in the course of sepsis (18h after injection of Escherichia coli). Our working hypothesis was that decreased production of cytokines caused by alcohol at this time would actually improve survival, because overproduction of pro-inflammatory mediators is thought to be the proximate cause of mortality in sepsis. Unexpectedly, administration of alcohol late in the course of sepsis led to a rapid increase in the number of viable bacteria in the peritoneal cavity. Significant increases in the concentrations of several cytokines and chemokines coincided with the increased number of bacteria in alcohol-treated mice and decreased survival time. These results demonstrated our working hypothesis to be incorrect, and reiterated the complexity of sepsis. Hypothermia is a consistent feature in this model of sepsis. In control mice (E.coli only), body temperature was near normal by 18h or 21h after administration of E.coli, but in mice treated with alcohol 18h after E.coli, hypothermia was significant 3h later and ultimately mortality was significantly increased. However, counteracting the hypothermic effect of alcohol by external warming of mice led to earlier mortality, demonstrating that hypothermia was not the major cause of mortality. These results, along with previous results from studies in which alcohol was given before initiation of sepsis, suggest that decreased cytokine and chemokine production may not be the key effect of alcohol that decreases resistance to sepsis. It seems more likely that suppression of mechanisms by which macrophages and neutrophils kill bacteria is critical, and this can occur even in the presence of high levels of cytokines and chemokines.