Chronic ethanol intake and burn injury: evidence for synergistic alteration in gut and immune integrity.

OBJECTIVE

Chronic ethanol (EtOH) intake and injury are both associated with increased susceptibility to infection in the host. This study examined the immune and gastrointestinal alterations induced by chronic EtOH intake and injury, and compared the effects of enteral and intravenous administration of EtOH.

DESIGN

Rats received 20% EtOH daily for 14 days by gavage [oral (PO)] or superior vena cava [intravenous (i.v.)] infusion. Mean blood EtOH concentrations at 90 minutes after administration were 95.3 mg/dL (PO) and 94.4 mg/dL (i.v.). An additional group of animals underwent a 30% total body surface area full-thickness burn injury 4 hours after the final dose of EtOH or normal saline on experimental day 14. All animals were killed 4 days after burn injury.

MATERIALS AND METHODS

Nonadherent splenic lymphocytes were tested for mitogenic responses to the T-cell mitogens concanavalin A (ConA) and phytohemagglutinin (PHA), and the B-cell mitogens lipopolysaccharide (LPS) and pokeweed. Quantitative bacterial cultures of mesenteric lymph nodes and liver were also performed. Alterations of intestinal mucosa were determined by measurement of ileal mucosal weight, DNA, protein, and diamine oxidase content. Circulating plasma endotoxin concentrations were also measured.

MEASUREMENTS AND MAIN RESULTS

Chronic PO-EtOH intake induced a significant impairment in mitogenic response to T-cell mitogens, with a fourfold reduction in ConA and a twofold reduction in PHA response (p < 0.05 by analysis of variance) and increased bacterial translocation (70% vs. 10%). Chronic EtOH administered by the i.v. route did not reduce mitogenic response to any of the mitogens studied. Histologic examination of ileal segments demonstrated that chronic PO-EtOH administration was associated with significant mucosal disruption and exfoliation. Chronic administration of PO-EtOH prior to burn injury induced a significant impairment in spleen mitogenic response to ConA, PHA, and LPS when compared with all other burn injury groups. Chronic administration of EtOH by the i.v. route prior to burn injury did not alter splenic mitogenesis. In addition, chronic PO-EtOH prior to burn injury increased bacterial translocation rates (80% vs. 33%) and prevented the normal intestinal reparative response to burn injury (demonstrated by a significant reduction in ileal mucosal weight, DNA, and diamine oxidase content).

CONCLUSIONS

Enteral but not i.v. administration of EtOH induced significant immunologic dysfunction (demonstrated by altered spleen mitogenic response) and gastrointestinal dysfunction (demonstrated by depressed ileal mucosal weight, DNA, and diamine oxidase content, and increased bacterial translocation rates). In addition, the administration of chronic enteral EtOH prior to injury resulted in significant immune suppression and impaired the host's ability for normal intestinal repair. These results suggest that this EtOH-induced reduction in immunocompetence may be gut-mediated and that the administration of alcohol prior to injury may result in a synergistic alteration of gut and immune integrity.