Gut-associated lymphoid T cell suppression enhances bacterial translocation in alcohol and burn injury

Abstract

The mechanism of alcohol-mediated increased infection in burn patients remains unknown. With the use of a rat model of acute alcohol and burn injury, the present study ascertained whether acute alcohol exposure before thermal injury enhances gut bacterial translocation. On day 2 postinjury, we found a severalfold increase in gut bacterial translocation in rats receiving both alcohol and burn injury compared with the animals receiving either injury alone. Whereas there were no demonstrable changes in intestinal morphology in any group of animals, a significant increase in intestinal permeability was observed in ethanol- and burn-injured rats compared with the rats receiving either injury alone. We further examined the role of intestinal immune defense by determining the gut-associated lymphoid (Peyer's patches and mesenteric lymph nodes) T cell effector responses 2 days after alcohol and burn injury. Although there was a decrease in the proliferation and interferon-gamma by gut lymphoid T cells after burn injury alone; the suppression was maximum in the group of rats receiving both alcohol and burn injuries. Furthermore, the depletion of CD3(+) cells in healthy rats resulted in bacterial accumulation in mesenteric lymph nodes; such CD3(+) cell depletion in alcohol- and burn-injured rats furthered the spread of bacteria to spleen and circulation. In conclusion, our data suggest that the increased intestinal permeability and a suppression of intestinal immune defense in rats receiving alcohol and burn injury may cause an increase in bacterial translocation and their spread to extraintestinal sites.

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: Summary of a symposium

“…Additionally, the finding of Kavanaugh et al (2005) showed that the combined insult significantly increases bacterial growth in the small intestine on day two after injury. The ethanol alone group exhibited an increase in intestinal permeability on day one and not on day two (Choudhry et al, 2002;Kavanaugh et al, 2005;Li et al, 2006). No change in other parameters was noted in the ethanol alone group.…”

“…However, on day two, the burn alone group exhibited a tendency of an increase in bacterial growth (though not significant), intestinal permeability and number of bacteria in the mesenteric lymph nodes, and a decrease in intestinal T cell functions. Nonetheless, the changes in these above parameters were more severe in the group of rats that has undergone a combined insult of alcohol and burn injury (Choudhry et al, 2002;Kavanaugh et al, 2005). These results suggest that acute alcohol intoxication potentiated the effect of burn injury on all of the parameters listed above including intestinal bacterial growth and permeability.…”

“…An analysis of various parameters on days one and two after injury revealed that the combined insult of ethanol and burn injury significantly increased intestinal permeability and the number of bacteria in mesenteric lymph nodes. Furthermore, the combined insult caused a significant decrease in intestinal T cell functions and their numbers in intestinal mucosa (Choudhry et al, 2002;Kavanaugh et al, 2005). Additionally, the finding of Kavanaugh et al (2005) showed that the combined insult significantly increases bacterial growth in the small intestine on day two after injury.…”

“…According to an estimate nearly one million people are affected with burn injuries every year within the United States and nearly half of these injuries occur under the influence of ethanol intoxication (Messingham et al, 2002;Choudhry and Chaudry, 2006). The effects of acute ethanol intoxication combined with burn injury were determined on intestinal bacterial growth, intestinal permeability, intestinal immune defense, and bacterial translocation (Choudhry et al, 2002;Kavanaugh et al, 2005;Li et al, 2006). Ethanol was administered to rats by gavage (5 ml of 20% ethanol) four hours prior to burn injury.…”

Sex differences and estrogen modulation of the cellular immune response after injury

“…Numerous studies have demonstrated the detrimental effect of ethanol on immune function including decreased lymphocyte activation following antigen-stimulation, decreased neutrophil infiltration and phagocytic capability, and altered cytokine production by both T cells and macrophages [86][87][88][89][90][91]. The immunosuppression caused by ethanol is exaggerated when in association with burn injury and can result in increased susceptibility to bacterial infection [92][93][94][95]. Consistent with immune suppression in males following burn plus alcohol, flutamide had no effect on immune responses in sham animals but restored cellular proliferation and the DTH response in burned male mice [33].…”