rial antagonism and/or enhancement of systemic and inIn acute liver failure following hepatitis, toxic insults, testinal mucosal immunity. (HEPATOLOGY 1997;25:642-or after major liver surgery, there is an increased bacte-647.) rial translocation from the gut. This may explain some of the infectious complications seen in these conditions. To elucidate mechanisms and find possible preventiveLactobacilli constitute an integral part of the normal gasmeasures, we investigated the effect of rectal administrointestinal microecology and are involved in host metabotration of arginine and probiotic bacteria (Lactobacillus lism. 1 They possess antimicrobial activities, including the spp.) on bacterial translocation and the extent of liver production of bacteriocin and low-molecular-weight antibiotic failure. Sprague-Dawley rats were used and five differsubstances, organic acids, and other metabolic end-products ent Lactobacillus strains (Lb. reuteri R2LC, Lb. rhamnoin both the human and animal gastrointestinal tract. 1-4 Lacsus DSM 6594 (Å strain 271), Lb. plantarum DSM 9843 tobacilli can inhibit the growth of various potentially patho-(Å strain 299v), Lb. fermentum 8704:3 (Å strain 245), and genic bacteria, 1,4,5 and they have been reported to be able to Lb. reuteri (Å strain 108) were administered rectally stimulate host immunity, 6 enhance the host resistance once daily for 8 days with and without 2% arginine.against infection and activate liver and peritoneal macroAcute liver injury (ALI) was induced on the eighth day phages, 7 and enhance intestinal immune function. [8][9][10] Bacteby intraperitoneal injection of D-galactosamine (1.1 g/kg riotherapy with lactobacilli, or other bacterial strains, has body weight), and samples were collected after 24 and been reported to be effective in both pseudomembranous and 48 hours. Bacterial translocation was evaluated by baculcerative colitis. 11-15 terial culture from portal and arterial blood, mesentericOn the other hand, the amino acid, arginine, has a potent lymph nodes, and liver tissue. Liver enzymes and bilirueffect on the immune system, particularly after trauma. 16 It bin were evaluated in the serum. The bacterial load in has a potent secretagogue effect on several endocrine glands, the cecum and colon was determined and the liver histoand these hormones may have a trophic effect on the intestipathological changes were studied. There was no mornal mucosa. [17][18][19] Furthermore, arginine is a known precursor tality at any time. The liver enzymes and bilirubin deof polyamines, which are considered important mediators of creased in some of the groups supplemented with cell growth and differentiation. 20 lactobacilli with and without arginine compared withThe L-arginine -nitric oxide pathway has been proposed to the ALI control group. The incidence of bacterial transbe the primary defense mechanism for killing intracellular location and the number of the translocated bacteria organisms, and to be the main mechanism of macrophage decreased significantly in some of the su...

Lipids and lipoproteins have emerged as key constituents of the immune response to microbial infection. We, therefore, sought to understand the complex interaction between lipoprotein metabolism and sepsis. Apolipoprotein E (apoE), a component of plasma lipoproteins, has been suggested to bind and traffic Ags for NKT cell activation. However, apoE’s role in sepsis has not been demonstrated. In this study, we examined the effect of exogenous apoE in a rat model of septic peritonitis, induced by cecal ligation and puncture. We demonstrate that 48 h after serial injections of apoE, septic mortality increased in a dose-dependent manner. While sepsis resulted in increased splenic and decreased hepatic and circulating NKT cell populations, serial injections of apoE for 24 h after cecal ligation and puncture increased the frequency, cell number, and BrdU uptake in splenic and hepatic NKT cell populations, while concomitantly depleting these populations in the circulation. These changes were correlated with elevated alanine amino transferase levels, an indicator of liver injury. Interestingly, while sepsis increased hepatic T cell apoptosis and necrosis, apoE reversed these changes. apoE also promoted increases in predominantly Th1 cytokine levels in sera and a decrease in IL-4, the main NKT cell-derived Th2 cytokine. Consequently, apoE treatment is associated with increased sepsis-induced mortality, and increased NKT cell frequency and proliferation in the liver and spleen, with concomitant decreases in these NKT cell parameters in the peripheral circulation. apoE treatment also promoted a Th1 cytokine response, increased the degree of liver injury, and decreased apoptosis in hepatic lymphocytes.

No abstract

Acute liver injury is associated with a high rate of infectious and septic complications. Most of these infections are produced by gram negative enteric bacteria. We evaluated bacterial translocation, intestinal permeability, blood flow, portal pressure, and intestinal microflora after induction of liver injury and 70% liver resection in the rat. The rate of translocation to both portal and arterial blood was 100% at 24 hours and 50% at 48 hours after liver resection compared with 83% to portal vein and 50% to aortic blood at both time points after acute liver injury. Translocation to intraabdominal organs (liver, spleen, and mesenteric lymph nodes) was 100% in both groups at both 24 and 48 hours. The rate of translocation increased after liver injury at 48 hours with progression of the liver injury but was decreased in the 70% liver resection group with improvement of liver function. "Total aerobic" and "total anaerobic" bacterial counts in small intestine and cecum were not affected. Pulmonary, distal small intestine, and cecal blood flow were decreased in both groups, whereas blood flow in the proximal small intestine was unaffected. Portal pressure and flow were increased after 70% liver resection, but they were decreased in acute liver injury. After acute liver injury, permeability of both distal small intestine and cecum increased, but after liver resection only cecal permeability increased. The results of this experiment show that bacterial translocation occurs in experimental acute liver injury and that its dynamic, pattern and fate are different from that observed after liver resection, which is a reversible surgical model of liver insufficiency.

Acute liver injury and hepatic failure are serious Acute liver injury is associated with a high rate of infectious and septic complications. Most of these infec-clinical conditions that are sometimes observed in extions are produced by gram negative enteric bacteria. tensive hepatic surgery and in patients with multiple We evaluated bacterial translocation, intestinal perme-system organ failure. 1,2 Bacterial infection and sepsis ability, blood flow, portal pressure, and intestinal mi-are recognized as dangerous complications of this remcroflora after induction of liver injury and 70% liver re-edy with significant share in its morbidity and mortalsection in the rat. The rate of translocation to both portal ity. [3][4][5] Gram-negative enteric bacteria are frequent and arterial blood was 100% at 24 hours and 50% at 48 causative organisms in most of the published studies. 6-8 hours after liver resection compared with 83% to portal It has been shown that the gut, as a reservoir of enteric vein and 50% to aortic blood at both time points after bacteria in the body, plays an important role in many acute liver injury. Translocation to intraabdominal orcritical clinical situations, such as major burns, hemorgans (liver, spleen, and mesenteric lymph nodes) was rhagic shock, and so on. 9 Under normal conditions a 100% in both groups at both 24 and 48 hours. The rate series of protective measures, such as mucosal barrier of translocation increased after liver injury at 48 hours with progression of the liver injury but was decreased function, immunoglobulin secretion, and local and sysin the 70% liver resection group with improvement of temic macrophage system prevent translocation of liver function. ''Total aerobic'' and ''total anaerobic'' bac-these potential pathogens to the extraintestinal sites. 10 terial counts in small intestine and cecum were not af-Severe clinical disorders may disrupt these normal profected. Pulmonary, distal small intestine, and cecal tective mechanisms and make it possible for the intestiblood flow were decreased in both groups, whereas nal bacteria to translocate. Translocation of endotoxin blood flow in the proximal small intestine was unaf-and intestinal bacteria in acute liver injury may intenfected. Portal pressure and flow were increased after sify the extent of injury and may also be responsible 70% liver resection, but they were decreased in acute for the high rate of associated infection and sepsis obliver injury. After acute liver injury, permeability of both served in these patients. So far, little attention has MATERIALS AND METHODSgery, Lund University, 221 85 Lund, Sweden. Experimental Groups.One hundred eight Sprague-