Napolitano L M, Koruda M J, Zimmerman K, McCowan K, Chang J, Meyer A A
Department of Surgery, University of North Carolina, Chapel Hill.
J Trauma. 1995 Feb;38(2):198-207. doi: 10.1097/00005373-199502000-00008.
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.
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.
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.
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).
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.
长期摄入乙醇（EtOH）及乙醇损伤均与宿主感染易感性增加有关。本研究检测了长期摄入乙醇及乙醇损伤所诱导的免疫和胃肠道改变，并比较了经肠内和静脉给予乙醇的效果。
大鼠通过灌胃[口服（PO）]或上腔静脉[静脉内（i.v.）]输注方式，每日接受20%乙醇，持续14天。给药后90分钟时的平均血乙醇浓度，口服组为95.3mg/dL，静脉内注射组为94.4mg/dL。在实验第14天，最后一剂乙醇或生理盐水给药4小时后，另一组动物接受30%体表面积的全层烧伤。所有动物在烧伤后4天处死。
检测非黏附性脾淋巴细胞对T细胞有丝分裂原刀豆蛋白A（ConA）和植物血凝素（PHA）以及B细胞有丝分裂原脂多糖（LPS）和商陆的促有丝分裂反应。还进行了肠系膜淋巴结和肝脏的定量细菌培养。通过测量回肠黏膜重量、DNA、蛋白质和二胺氧化酶含量来确定肠黏膜的改变。同时检测循环血浆内毒素浓度。
长期口服乙醇导致对T细胞有丝分裂原的促有丝分裂反应显著受损，ConA反应降低四倍，PHA反应降低两倍（方差分析，p<0.05），且细菌移位增加（70%对10%）。静脉内给予乙醇未降低对所研究的任何有丝分裂原的促有丝分裂反应。回肠段的组织学检查表明，长期口服乙醇与显著的黏膜破坏和剥脱有关。与所有其他烧伤组相比，烧伤前长期口服乙醇导致脾脏对ConA、PHA和LPS的促有丝分裂反应显著受损。烧伤前静脉内给予乙醇未改变脾脏的有丝分裂活性。此外，烧伤前长期口服乙醇增加了细菌移位率（80%对33%），并阻止了肠道对烧伤的正常修复反应（表现为回肠黏膜重量、DNA和二胺氧化酶含量显著降低）。
经肠内而非静脉内给予乙醇可诱导显著的免疫功能障碍（表现为脾脏促有丝分裂反应改变）和胃肠道功能障碍（表现为回肠黏膜重量、DNA和二胺氧化酶含量降低以及细菌移位率增加）。此外，损伤前长期经肠内给予乙醇导致显著的免疫抑制，并损害宿主肠道正常修复能力。这些结果表明，乙醇诱导的免疫能力降低可能是由肠道介导的，且损伤前给予酒精可能导致肠道和免疫完整性的协同改变。
