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PubMed2005

Oro-facial granulomatosis: Crohn's disease or a new inflammatory bowel disease?

BACKGROUND: Oro-facial granulomatosis (OFG) is a rare chronic inflammatory disorder presenting characteristically with lip swelling but also affecting gingivae, buccal mucosa, floor of mouth, and a number of other sites in the oral cavity. Histologically, OFG resembles Crohn's disease (CD), and a number of patients with CD have oral involvement identical to OFG. However, the exact relationship between OFG and CD remains unknown. METHODS: Thirty-five patients with OFG and no gut symptoms were identified from a combined oral medicine/gastroenterology clinic. All underwent a standardized assessment of the oral cavity and oral mucosal biopsy to characterize the number of sites affected and the type of inflammation involved. Hematological and biochemical parameters were also recorded. All 35 patients underwent ileocolonoscopy and biopsy to assess the presence of coexistent intestinal inflammation. RESULTS: Ileal or colonic abnormalities were detected in 19/35 (54%) cases. From gut biopsies, granulomas were present in 13/19 cases (64%). An intestinal abnormality was significantly more likely if the age of OFG onset was less than 30 years (P=0.01). Those with more severe oral inflammation were also more likely to have intestinal inflammation (P=0.025), and there was also a correlation between the histologic severity of oral inflammation and the histologic severity of gut inflammation (P=0.047). No relationship was found between any blood parameter and intestinal involvement. CONCLUSIONS: Endoscopic and histologic intestinal abnormalities are common in patients with OFG with no gastrointestinal symptoms. Younger patients with OFG are more likely to have concomitant intestinal involvement. In these patients, granulomas are more frequent in endoscopic biopsies than reported in patients with documented CD. OFG with associated intestinal inflammation may represent a separate entity in which granulomatous inflammation occurs throughout the gastrointestinal tract in response to an unknown antigen or antigens.

Adolescent↗
PubMed2002

CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice.

Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal immune response with elevated levels of the Th1 cytokines TNF, IL-12 and IFN-gamma. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic intestinal inflammation by as yet unknown mechanisms. Bacterial DNA contains unmethylated cytosine-guanosine dinucleotides (CpG) which strongly activate Th1-mediated immune responses. To test whether these CpG-motifs contribute to intestinal inflammation we treated mice with dextran-sulfate-sodium (DSS)-induced acute or chronic colitis for 5 days with CpG-containing oligodeoxynucleotides (CpG-ODN). Colonic inflammation was assessed by histological scoring. Colonic cytokine RNA was quantified by reverse transcription-PCR and cytokine secretion from mesenterial lymph node cells by ELISA. In chronic colitis, CpG-ODN treatment severely aggravated inflammation by 50%. Colonic expression of IFN-gamma and TNF was elevated (200- and 150-fold, respectively) and IFN-gamma and IL-12 secretion from lymph node cells was increased 5,000- and 8-fold, respectively, compared to GpG-ODN-treated controls. Similar effects were obtained in acute colitis. In conclusion, CpG-motifs of bacterial DNA have proinflammatory activity by strengthening the Th1 arm of immunity in DSS-induced colitis, and might therefore play a significant role in the initiation and perpetuation of inflammation in IBD.

Acute Disease↗
PubMed2003

OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice.

Interactions between APC and T lymphocytes have been implicated as a major factor contributing to inflammatory bowel disease. To test whether OX40/OX40L interaction plays a role in chronic intestinal inflammation, we induced chronic colitis using dextran sulfate sodium and treated the mice with a murine fusion protein (OX40-IgG). Treatment resulted in a dose-dependent and significant reduction of intestinal inflammation (46%) as measured by a histologic score. IL-10 and IL-5 production from mesenteric lymph node cells increased 20-fold and 18-fold, respectively. In colonic tissue, IL-10 mRNA levels increased and the expression of T-bet was decreased to 30%. IL-10 neutralization partly inhibited the beneficial effects of OX40-IgG treatment. Surprisingly, despite the reduction of inflammation we found the number and size of colonic lymphoid follicles increased, with an accumulation of CD4(+) cells in the mantle area. In contrast, the number of CD4(+) cells infiltrating the mucosa was significantly reduced, as was their CXCR5 expression (24-fold). We conclude that OX40/OX40L interaction contributes to the perpetuation of chronic colitis partly by suppressing IL-10 production. Furthermore, our data suggest that the OX40/OX40L-induced CXCR5 expression on CD4(+) cells may be important for the inflammatory process by allowing migration to the germinal center for further differentiation of CD4(+) cells before they infiltrate the chronically inflamed mucosa.

Animals↗
PubMed2006

4-Hydroxynonenal modifies IgA in rat intestine after lipopolysaccharide injection.

The lipid peroxide 4-hydroxynonenal (HNE) was measured in rat intestinal mucosa after lipopolysaccharide (LPS) injection (0.5 mg/kg, ip) by a highly sensitive time-resolved fluoroimmunoassay. HNE was increased, with a small peak at 20 min followed by a sustained elevation at 2-4 h, after injection of LPS. Immunohistochemistry demonstrated enhanced labeling with anti-IgA and anti-HNE antibodies in the plasma cells followed by diffusion of the labeled materials into the submucosal tissue after LPS injection. Immunoprecipitation with anti-IgA antibody and Western blotting with anti-HNE antibody showed that IgA is modified with HNE after LPS injection. The HNE (5 microM-5 mM) modification in vitro reduced the bactericidal activity of IgA and anti-Escherichia coli serum. The HNE modification in vitro also promoted polymerization of IgA as shown by nondenaturing gel electrophoresis. This is the first demonstration of the modification of IgA with HNE in an in vivo model of intestinal inflammation as well as in vitro effects of HNE on bactericidal activity and polymerization of IgA. These findings will help in understanding the involvement of oxidative stress in the IgA-mediated immune response exerted by plasma cells in early intestinal inflammation.

Aldehydes↗
PubMed2002

[Effect of Pentavac and MMR vaccination on the intestine.].

OBJECTIVE: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. AIM: To assess if MMR vaccination is associated with sub-clinical intestinal inflammation which is central to the autistic "enterocolitis" theory. The study was not designed to test directly the association of autism to MMR vaccination. MATERIAL AND METHODS: We studied 109/20 infants, before and two and four weeks after immunization with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). RESULTS: Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. CONCLUSIONS: The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis.

English Abstract↗
PubMed1992

Effects of f-Met-Leu-Phe-induced inflammation on intestinal lymph flow and lymphatic pump behavior.

Previous studies in the literature indicate that intraenteric placement of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) evokes an intestinal inflammatory response characterized by an accumulation of interstitial fluid and increased lymph flow. Furthermore, it is known that movement of lymph away from the intestine is dependent on the rhythmic pumping of lymph by collecting lymphatics in the mesentery. The purpose of the present study was to determine whether the f-Met-Leu-Phe-induced increase in lymph formation is countered by an increase in lymphatic pump efficiency. Male Sprague-Dawley rats were anesthetized, and a segment of ileum with adjacent mesentery was exteriorized. The mesentery was positioned over an optical window, and a 100-microns collecting lymphatic was selected for study. The preparation was transferred to a video microscope, and the activity of the lymphatic pump was monitored under control conditions and during intraluminal infusion of 1 microM f-Met-Leu-Phe. Lymph propulsion by the lymphatic pump was calculated from the product of stroke volume and contraction frequency. In one group of animals, total lymph flow was determined by cannulating the lymphatic draining the ileal segment. Total lymph flow increased following f-Met-Leu-Phe placement in the intestine. The increased lymph flow was paralleled by a rise in lymphatic pumping. The rise in lymph propulsion by the lymphatic pump resulted exclusively from an increased stroke volume, inasmuch as contraction frequency did not change. The results of the present study suggest that activation of the lymphatic pump during acute inflammation may be important in preventing interstitial edema.

Animals↗
PubMed2006

Flag in the crossroads: flagellin modulates innate and adaptive immunity.

PURPOSE OF REVIEW: To consider observations suggesting that the bacterial protein flagellin, the primary structural component of flagella, plays a major role in mediating gut inflammation associated with infection by enteric pathogens and in inflammatory bowel disease. RECENT FINDINGS: Biochemical dissection of an in-vitro model of bacterial-epithelial interactions revealed flagellin, via ligation of Toll-like receptor 5, to be a major means of activating the innate immune responses defining active intestinal inflammation. Application of the novel technique of serologic expression cloning to murine models of colitis discovered that flagellin is also a dominant target of the adaptive immune responses that drive colitis in such models. Human studies observed that flagellin was also a major antigenic target of immune responses associated with Crohn's disease. Carriers of dominant-negative Toll-like receptor 5 gene exhibit reduced natural acquisition of immunity to flagellin, indicating that the adaptive immune response to flagellin is likely driven, in part, by Toll-like receptor 5. In some genetic backgrounds dominant-negative Toll-like receptor 5 associated negatively with Crohn's disease, suggesting that immune responses to flagellin are not only associated with Crohn's disease, but can promote the pathogenic response. SUMMARY: Flagellin is a major activator of innate immunity thus driving pathogen-induced acute inflammation and, perhaps, the active flares of inflammatory bowel disease. Flagellin is also a dominant antigen of the Crohn's disease-associated adaptive immune response, thus placing this molecule at the crossroads of the innate and adaptive immune responses that are the hallmark of intestinal inflammation.

Adaptation, Physiological↗
PubMed2002

Review article: a critical approach to new forms of treatment of Crohn's disease and ulcerative colitis.

Most patients with inflammatory bowel disease can be managed with conventional immunosuppressive therapy. The choice of agents to prevent relapses of inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies in animal models of inflammatory bowel disease indicate that chronic intestinal inflammation results from enhanced immune responses to bacteria that are present normally in the lumen. Loss of tolerance, an abnormal function or defective healing of the mucosal barrier may all give raise to chronic intestinal inflammation. This hypothesis is the basis of new therapies aimed at either decreasing the levels of luminal bacterial antigens and/or selectively blocking detrimental mucosal immune responses. Anti-TNF is an example of this novel approach that is very effective in Crohn's disease. The use of biological therapy is costly, however, and the long-term complications are not yet known. The recent increase of tuberculosis in patients treated with anti-TNF indicates that careful monitoring is necessary. It is clear that the new forms of treatment may play an important role in tailoring the appropriate drug to a specific group of patients. However, for the time being, fine-tuning in the use of conventional immunosuppression is necessary. New knowledge in the pharmacogenetics of these compounds allows improvements to be made in their use. It is to be hoped that a critical approach in the use of current and future drugs, taking into account the advances in the aetiopathogenesis of inflammatory bowel disease, will contribute to the quality of life of patients with inflammatory bowel disease.

Antibodies, Monoclonal↗
PubMed2003

Mast cells are required for experimental oral allergen-induced diarrhea.

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum-sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti-c-kit mAb), anti-IgE treatment, and Fc epsilon RI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.

Allergens↗
PubMed2001

Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice.

1. We have studied the effect of palmitoylethanolamide (PEA, 2.5 - 30 mg kg(-1), i.p.) on upper gastrointestinal transit in control mice and in mice with chronic intestinal inflammation induced by croton oil. 2. PEA significantly and dose-dependently decreased intestinal transit. The inhibitory effect of PEA (10 mg kg(-1)) was not modified by the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg kg(-1), i.p.), the cannabinoid CB(2) receptor antagonist SR144528 (1 mg kg(-1), i.p.), N(G)-nitro-L-arginine methyl ester (L-NAME, 25 mg kg(-1), i.p.), yohimbine (1 mg kg(-1), i.p.), naloxone (2 mg kg(-1), i.p.) or hexamethonium (1 mg kg(-1), i.p.). 3. PEA levels were significantly decreased in the small intestine of croton oil-treated mice. In these animals, PEA also inhibited motility and this effect was not counteracted by SR141716A (0.3 mg kg(-1)), or SR144528 (1 mg kg(-1)). 4. Pre-treatment of mice with the amidase inhibitor phenylmethyl sulphonil fluoride (PMSF, 30 mg kg(-1), i.p.) did not modify the inhibitory effect of PEA, either in control or in mice with inflammation. 5. It is concluded that PEA inhibits intestinal motility with a peripheral mechanism independent from cannabinoid receptor activation. The decreased levels of PEA in croton oil-treated might contribute, at least in part, to the exaggerated transit observed during chronic intestinal inflammation.

Adrenergic alpha-Antagonists↗
PubMed1995

Genetic and spontaneous models of inflammatory bowel disease in rodents: evidence for abnormalities in mucosal immune regulation.

A number of models of spontaneous chronic intestinal inflammation in mice and rats have recently been developed. A characteristic of the majority of these models is that disease developed as a consequence of immune manipulations, suggesting a central role for the immune system in the regulation of intestinal inflammation. Analysis of cytokine patterns in disease showed elevations in TNF-alpha and IFN-gamma, characteristic of the T-helper-1 (Th1) pathway, implicating Th1 cells and their cytokines in disease pathogenesis. Strikingly, inflammation did not develop in mice maintained in germ-free conditions, suggesting disease may develop due to a dysregulated inflammatory response to components of the normal flora. Evidence from a number of these models suggests that this potentially pathogenic inflammatory response does not develop in normal animals as it is actively inhibited by a population of CD4+ alpha beta + regulatory T cells and immunosuppressive cytokines such as IL-10 and TGF-beta 1. These new models will allow further investigation into the mechanisms of natural immune regulation and protection in the intestinal tract and how these mechanisms relate to the etiopathogenesis of inflammatory bowel disease (IBD). Furthermore, these models should provide useful insights for the design of effective immunomodulatory therapies for the treatment of IBD in humans.

Animals↗
PubMed2003

Effect of the antioxidant Mesna (2-mercaptoethane sulfonate) on experimental colitis.

Reactive oxygen species play a key role in intestinal inflammation, although interventional studies using antioxidants have shown only weak beneficial effects both in humans and animals. Hence, our aim was to examine the possible beneficial effect of the antioxidant 2-mercaptoethane sulfonate (Mesna) on experimental colitis. Colitis was induced in rats by intrarectal instillation of trinitrobenzene sulfonic acid (TNB) followed immediately by intrarectal Mesna or saline, administered for 14 days, twice daily. A beneficial effect of Mesna was observed, resulting in a significant reduction in inflammation followed by almost full recovery. iNOS mRNA expression and myeloperoxidase (MPO) activity were significantly increased in the TNB-Mesna group. These results suggest that the induction of iNOS in the presence of Mesna reduced intestinal inflammation. Mesna probably resolved this inflammation by scavenging reactive oxygen species generated by the augmented infiltration of polymorphonuclear leukocytes.

Animals↗
PubMed2002

Prevalence of ankylosing spondylitis and other spondyloarthropathies among patients with inflammatory bowel disease: a population study (the IBSEN study).

OBJECTIVE: To study the occurrence of spondyloarthropathies (SpA) in patients with inflammatory bowel disease (IBD) seen 6 years after IBD diagnosis. METHODS: In a population based cohort of 654 patients with IBD, 521 patients (80%) were investigated, which included a complete rheumatological examination. Radiographs of the sacroiliac joints and lumbar spine were performed in 406 of these patients (78%). The development of SpA was analyzed with regard to the presence of HLA-B27, duration of IBD symptoms, and the extent of intestinal inflammation. RESULTS: The occurrence of ankylosing spondylitis (AS) was 2.6% in ulcerative colitis and 6% in Crohn's disease (p = 0.08), yielding an overall prevalence of 3.7% in IBD. No correlation between localization or extent of the intestinal inflammation and presence of AS was found. HLA-B27 was present in 73% of cases with AS. The overall prevalence of SpA was 22%. Inflammatory back pain without AS (IBP) was found in 18% of the patients. Typical features of SpA were rare, while fibromyalgia was common in IBP, indicating that IBP is not a precursor or manifestation of SpA in patients with IBD. The prevalence of radiological sacroiliitis without clinical features of SpA was 2.0%. CONCLUSION: AS occurred frequently in patients with newly diagnosed IBD. IBP did not seem to predispose to AS or other forms of SpA. The overall prevalence of SpA was 22%, whereas the prevalence of asymptomatic radiological sacroiliitis was low.

Adolescent↗
PubMed2000

Effects of hydrogen peroxide scavenger Catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease.

This study was conducted to quantify the effect of systemic Catalase, a hydrogen peroxide scavenger, on villous microcirculation in the inflamed small intestine of the rat. Intestinal inflammation was induced with s.c. application of Indomethacin. Intravital fluorescence microscopy and FITC-labeled erythrocytes were used to quantify erythrocyte velocity and arteriolar diameter in the main arteriole of the villi in the terminal ileum following i.v. application of Catalase in the inflamed intestine, and the blood flow was calculated. Control groups were formed for Ringer's lactate, Catalase and Indomethacin, respectively. We found that villous blood flow was significantly increased in the in the inflamed intestine. Application of Catalase led to a significant decrease in villous perfusion, but had no effect in the control group. The increase in villous blood flow was accompanied by changes in the diameter of the main arteriole. This effect on arteriolar diameter was reversed by i.v. Catalase. Our results provide evidence that systemic application of Indomethacin leads to vasodilatation of the main arteriole of the villus in the rat ileum and hyperemia in the mucosa. Hyperemia and the vascular diameter of the main arteriole were significantly reduced by H(2)O(2)-scavenger Catalase, suggesting that endogenous H(2)O(2) may be one of the mediators of hyperemia in the mucosa in this animal model of intestinal inflammation.

Animals↗
PubMed2002

Prebiotic treatment of experimental colitis with germinated barley foodstuff: a comparison with probiotic or antibiotic treatment.

There is increasing evidence that intestinal microflora play an important role in the pathogenesis of ulcerative colitis. Therefore, modification of the microflora by prebiotics, probiotics, and antibiotics may be a rational approach for controlling intestinal inflammation. Germinated barley food-stuff (GBF) is an insoluble mixture of glutamine-rich protein and hemicellulose-rich dietary fiber. GBF is utilized efficiently by Bifidobacterium, Lactobacillus, and Eubacterium and converted by them into lactate, acetate, and butyrate. These bacterial organic acids preserve a favorable intestinal condition. We have previously shown that GBF has attenuated intestinal inflammation in patients with ulcerative colitis and experimental colitis models through prebiotic actions. The aim of this study was to compare the effect of GBF with that of probiotics and antibiotics in an experimental colitis model. Colitis was induced by feeding male SD rats with a diet containing 3.0-3.5% dextran sodium sulfate (DSS). The therapeutic effect of oral administration of a prebiotic (GBF), probiotics (mixture of Lactobacillus and Clostridium butyricum), antibiotics (vancomycin, metronidazole), and the vehicle was determined by assessing clinical and pathological scores on day 6 after initiation of colitis. Butyrate concentrations in the cecal content were also determined. GBF treatment significantly reduced colonic inflammation as assessed by clinical scores with an increase in cecal butyrate levels. Probiotic treatment with a mixture of Lactobacillus and Clostridium butyricum did not show such an effect. Both antibiotic treatments significantly attenuated clinical and pathological scores. However, in contrast to GBF, this treatment led to a significant decrease in cecal butyrate levels. These data suggest that modification of the intestinal microflora by prebiotics, including GBF, may serve as a useful adjunct in the treatment of ulcerative colitis as well as antibiotic treatment.

Animal Feed↗
PubMed2002

Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation.

B cells possess a variety of immune functions that are involved in normal and abnormal immune responses, including autoimmune disorders. Through murine models of intestinal inflammation, we here demonstrate a B cell subset that is induced in gut-associated lymphoid tissues and is characterized by CD1d upregulation. This B cell subset appears under a chronic inflammatory environment, produces IL-10, and suppresses progression of intestinal inflammation by downregulating inflammatory cascades associated with IL-1 upregulation and STAT3 activation rather than by altering polarized T helper responses. This study indicates that B cells, by producing cytokines such as IL-10, can act as regulatory cells in immunologically mediated inflammatory reactions.

Animals↗
PubMed2002

Suppression of intestinal ischemia-reperfusion injury by a specific peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, in rats.

Neutrophil activation and tumor necrosis factor-alpha (TNF-alpha) induction play a critical role in ischemia-reperfusion-induced intestinal inflammation. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a member of the nuclear hormone receptor superfamily, has recently been implicated as a regulator of inflammatory responses. The aim of the present study was to determine whether pioglitazone, a specific PPAR-gamma ligand, can ameliorate reperfusion-induced intestinal injury in rats, and whether the agent can inhibit the increase in neutrophil accumulation associated with TNF-alpha expression. Intestinal damage was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 30 min followed by reperfusion. Reperfusion after 30 min ischemia resulted in an increase in luminal protein concentrations with levels reaching a maximum after 60 min of reperfusion. In contrast, pretreatment with pioglitazone 2 h before ischemia inhibited the increase in luminal protein concentrations after 60 min reperfusion in a dose-dependent manner (1-30 mg/kg). The increase in tissue-associated myeloperoxidase activity, an index of neutrophil infiltration, after reperfusion was significantly inhibited by pretreatment with pioglitazone. Pioglitazone also inhibited increases in intestinal TNF-alpha protein and mRNA expression determined by ELISA and RT-PCR, respectively. In conclusion, activation of PPAR-gamma may represent a novel approach to the treatment of intestinal inflammation induced by ischemia-reperfusion.

Animals↗
PubMed2003

Ethyl pyruvate provides durable protection against inflammation-induced intestinal epithelial barrier dysfunction.

Ethyl pyruvate (EP) has been shown to be an effective anti-inflammatory agent. Herein, we sought to test the following hypotheses: 1) the pharmacological effects of EP persist after cells have been exposed to the compound in vitro, even if the cultures are washed to minimize the amount of EP that is retained in the media; 2) the pharmacological effects of EP persist in vivo, even after waiting a prolonged period (i.e., 6 h) after the last dose of the compound; and 3) the in vivo pharmacological effects of EP are distinct from those of the closely related compound, sodium pyruvate. Incubation of Caco-2 human enterocyte-like monolayers with cytomix, a mixture of interleukin-1beta, interferon-gamma, and tumor necrosis factor, increased permeability to the fluorescent macromolecule, FITC-labeled Dextran (mol wt 4,000 Da). Co-incubation of the cells with 5 mM EP ameliorated cytomix-induced hyperpermeability and induction of iNOS mRNA expression. EP was associated with similar pharmacological effects when cells were pre-incubated with the compound for 24 h prior and then washed extensively prior to adding the cytokine cocktail. Injecting C57Bl/6 mice with lipopolysaccharide (LPS) resulted in gut barrier dysfunction and hepatocellular injury. Although equivalent doses of both EP and sodium pyruvate ameliorated these phenomena, EP was more efficacious than pyruvate. Pretreatment with EP ameliorated the deleterious effects of LPS, even when the duration between the last dose of EP and the endotoxic challenge was 6 h. We conclude that EP provides durable protection against some of the deleterious effects of LPS or pro-inflammatory cytokines.

Animals↗