Forms Of Intestinal Inflammation Research Articles

Protective effects of rice bran fermented by Saccharomyces cerevisiae Misaki-1 and Lactobacillus plantarum Sanriki-SU8 in dextran sodium sulphate-induced inflammatory bowel disease model mice

Abstract Inflammatory bowel disease (IBD) is characterised by two forms of intestinal inflammation: ulcerative colitis (UC) and Crohn’s disease (CD). Oxidative stress is considered as one of the etiological factors involved in several signals and symptoms of IBD. Rice bran (RB) is a major by-product of rice polishing. In this study, the effect of fermentation by Lactobacillus plantarum S-SU8 and Saccharomyces cerevisiae Misaki-1 at 30 °C for 2 days on the antioxidant and anti-IBD properties, as well as the DPPH and O 2 − radical scavenging capacities, of the aqueous extract suspension (AES) of RB was evaluated. No significant effects were observed. The inhibitory effect of RB AES on lipopolysaccharide-induced nitric oxide (NO) secretion of murine macrophage RAW264.7 cells was also unaffected. However, the fermented RB AES, compared with intact RB AES, clearly showed the protective effects in dextran sodium sulphate (DSS)-induced IBD model mice.

Gallic acid suppresses inflammation in dextran sodium sulfate-induced colitis in mice: Possible mechanisms

Inflammatory bowel diseases (IBD) encompass at least two forms of intestinal inflammation: Crohn's disease and ulcerative colitis (UC). Both conditions are chronic and inflammatory disorders in the gastrointestinal tract, with an increasing prevalence being associated with the industrialization of nations and in developing countries. Patients with these disorders are 10 to 20 times more likely to develop cancer of the colon. The aim of this study was to characterize the effects of a naturally occurring polyphenol, gallic acid (GA), in an experimental murine model of UC. A significant blunting of weight loss and clinical symptoms was observed in dextran sodium sulfate (DSS)-exposed, GA-treated mice compared with control mice. This effect was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity, and a decrease in the expression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and pro-inflammatory cytokines. In addition, GA reduced the activation and nuclear accumulation of p-STAT3Y705, preventing the degradation of the inhibitory protein IκB and inhibiting of the nuclear translocation of p65-NF-κB in colonic mucosa. These findings suggest that GA exerts potentially clinically useful anti-inflammatory effects mediated through the suppression of p65-NF-κB and IL-6/p-STAT3Y705 activation.

Colitis and Fistulizing Disease in Patient with History of Pelvic Radiation for Gynecologic Malignancy. Could this be Inflammatory Bowel Disease?

Purpose: A 50 year Caucasian female was referred to our gastroenterology clinic for evaluation of a rectal fistula. Her past medical history is significant for a diagnosis of cervical cancer 18 years ago for which she was treated with pelvic radiation. One year later she was subsequently found to have vaginal cancer; underwent pelvic exoneration which included TAH-BSO, removal of bladder and partial colectomy (amount), which resulted in a urostomy and colostomy. Seventeen years post surgery, patient has complaints of passing urine through rectum for 4 month and noticed the passage of mucus through her colostomy, however did not notice increased colostomy output. She denied abdominal pain, rectal bleeding, fever or chills. Laboratory data showed hemoglobin of 11.9, MCV 92, normal chemistries and liver function tests, including normal albumin. PET scan showed no metastasis or residual cancer. CT abdomen and pelvis showed a fistulous connection between her left ureter and recto-sigmoid area of her colon. A colonoscopy was performed through rectal stump and ostomy. A small opening was seen in rectum suspicious for a fistula. Rectal mucosa showed mild erythema and friability. Only 30cm of colon was encountered with erythema and friability in the cecum and the remaining colon appearing endoscopically normal. Colonic biopsies revealed chronic active colitis, crypt distortion and focal acute cryptitis. The terminal ileum appeared normal, however biopsy showed mild ileitis. IBD serology revealed a pattern consistent with IBD, specifically Crohn's disease. Given patient's history; radiation induced colitis with fistulization is the most likely diagnosis, however this case illustrates her endoscopic, pathologic and serologic findings are not specific to radiation colitis. A review of the literature was done to see if other than this patient's history if there are any distinguishing features to make a diagnosis of radiation colitis versus inflammatory bowel disease, and if this delineation between the two causes of intestinal inflammation would alter the patient's management. Currently no gold standard test exists for the diagnosis of IBD. For this reason, diagnosing IBD continues to be at times a diagnostic challenge for the gastroenterologist. Distinguishing among various forms of intestinal inflammation will remain a trial of clinical judgment; using relevant history, physical examination, laboratory testing, and detailed review of radiographic, endoscopic, and pathologic data.

Bacteria-free solution derived from lactobacillus plantarum inhibits multiple NF-kappaB pathways and inhibits proteasome function

Bacteria play a role in inflammatory bowel disease and other forms of intestinal inflammation. Although much attention has focused on the search for a pathogen or inciting inflammatory bacteria, another possibility is a lack of beneficial bacteria that normally confer anti-inflammatory properties in the gut. The purpose of this study was to determine whether normal commensal bacteria could inhibit inflammatory pathways important in intestinal inflammation. Conditioned media from Lactobacillus plantarum (Lp-CM) and other gut bacteria was used to treat intestinal epithelial cell (YAMC) and macrophage (RAW 264.7) or primary culture murine dendritic cells. NF-kappaB was activated through TNF-Receptor, MyD88-dependent and -independent pathways and effects of Lp-CM on the NF-kappaB pathway were assessed. NF-kappaB binding activity was measured using ELISA and EMSA. 1kappaB expression was assessed by Western blot analysis, and proteasome activity determined using fluorescence-based proteasome assays. MCP-1 release was determined by ELISA. Lp-CM inhibited NF-kappaB binding activity, degradation of IkappaBalpha and the chymotrypsin-like activity of the proteasome. Moreover, Lp-CM directly inhibited the activity of purified mouse proteasomes. This effect was specific, since conditioned media from other bacteria had no inhibitory effect. Unlike other proteasome inhibitors, Lp-CM was not toxic in cell death assays. Lp-CM inhibited MCP-1 release in all cell types tested. These studies confirm, and provide a mechanism for, the anti-inflammatory effects of the probiotic and commensal bacterium Lactobacillus plantarum. The use of bacteria-free Lp-CM provides a novel strategy for treatment of intestinal inflammation which would eliminate the risk of bacteremia reported with conventional probiotics.

IL-4 gene transfer to the small bowel serosa leads to intestinal inflammation and smooth muscle hyperresponsiveness

Intestinal mucosal inflammation can lead to altered function of the underlying smooth muscle, which becomes hyperreactive to most contractile stimuli. Through nematode parasite infection models, T helper type 2 (Th2) cytokines have been implicated in intestinal muscle dysfunction; however, the mechanisms involved and the relevance of these findings to other forms of intestinal inflammation are unclear. Through gene transfer, we explored whether the Th2 cytokine IL-4 can mediate changes in longitudinal muscle function in the context of an adenoviral infection. Following abdominal surgery on mice, control beta-galactosidase-encoding recombinant adenoviruses and IL-4-encoding adenoviruses were applied to the serosal surface of the jejunum, leading to infection of cells in the serosa and in the mesentery. Marker transgene expression lasted for 3 wk and was accompanied by the recruitment of macrophages, lymphocytes, and neutrophils into the peritoneal cavity and mild inflammation at the site of infection. IL-4 transgene expression led to a stronger inflammatory response characterized by tissue eosinophilia and increased numbers of peritoneal mast cells and plasma cells. Whereas control virus infection had no effect on intestinal muscle function, infection with the IL-4 virus led to significant jejunal muscle hypercontractility, evident by day 7 postinfection. This modulation of smooth muscle function was shown to be IL-4 specific, since the application of an IL-5-encoding adenovirus induced tissue eosinophilia but did not alter muscle function. These results highlight an important causal role for IL-4 in the pathological regulation of enteric smooth muscle function and identify a novel strategy for gene transfer to the intestine.

Human mucosa/submucosa interactions during intestinal inflammation: involvement of the enteric nervous system in interleukin-8 secretion

Interleukin-8 (IL-8) is a key chemokine upregulated in various forms of intestinal inflammation, especially those induced by bacteria such as Clostridium difficile (C. difficile). Although interactions between different mucosal and submucosal cellular components have been reported, whether such interactions are involved in the regulation of IL-8 secretion during C. difficile infection is unknown. Moreover, whether the enteric nervous system, a major component of the submucosa, is involved in IL-8 secretion during an inflammatory challenge remains to be determined. In order to investigate mucosa/submucosa interactions that regulate IL-8 secretion, we co-cultured human intestinal mucosa and submucosa. In control condition, IL-8 secretion in co-culture was lower than the sum of the IL-8 secretion of both tissue layers cultured alone. Contrastingly, IL-8 secretion increased in co-culture after mucosal challenge with toxin B of C. difficile through an IL-1 beta-dependent pathway. Moreover, we observed that toxin B of C. difficile increased IL-8 immunoreactivity in submucosal enteric neurones in co-culture and in intact preparations of mucosa/submucosa, through an IL-1 beta-dependent pathway. IL-1 beta also increased IL-8 secretion and IL-8 mRNA expression in human neuronal cell lines (NT2-N and SH-SY5Y), through p38 and ERK1/2 MAP kinase-dependent pathways. Our results demonstrate that mucosa/submucosa interactions regulate IL-8 secretion during inflammatory processes in human through IL-1 beta-dependent pathways. Finally we observed that human submucosal neurones synthesize IL-8, whose production in neurones is induced by IL-1 beta via MAPK-dependent pathways.

Signal Transducers and Activators of Transcription 3 Signaling Pathway

Crohn's disease (CD) and ulcerative colitis (UC), the two major forms of chronic inflammatory bowel disease (IBD), are characterized by mucosal immune cell activation that is driven by a cytokine imbalance. Several cytokines involved in IBD act through the activation of the signal transducers and activators of transcription (STAT) family. We investigated the activation of STAT3 in the mucosa of CD and UC patients, and evaluated whether this event is specific for IBD patients. Using immunofluorescence and immunoblotting, total and phosphorylated STAT3 levels were assessed in biopsy specimens, isolated lamina propria mononuclear cells, and peripheral blood mononuclear cells from patients with CD, UC, other forms of intestinal inflammation, and control subjects. Immunoblotting revealed phosphorylated STAT3 in mucosal biopsy specimens from patients with CD, UC, celiac disease, and acute self-limited colitis, but not in the normal mucosa of control subjects. In IBD patients, STAT3 activation was confined to actively inflamed areas. Accordingly, activated STAT3 was detected in isolated lamina propria mononuclear cells from inflamed IBD tissues, but not in peripheral blood mononuclear cells from control subjects or IBD patients. Immunofluorescence demonstrated that the sources of activated STAT3 were macrophages and T lymphocytes, but not neutrophils. STAT3 activation also was detected in T cells infiltrating the duodenal mucosa of celiac disease patients. We conclude that STAT3 signaling occurs in both CD and UC, where it is strictly confined to areas of active inflammation and is limited to infiltrating macrophages and T cells. The occurrence of STAT3 signaling in other acute and chronic intestinal inflammatory conditions suggests that, rather than a specific feature of IBD, it represents a fundamental signaling pathway that is shared by multiple forms of gut inflammation.

From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation

Inflammation is the gut’s mute response to a myriad of diverse insults. Assigning a diagnosis in such cases is often straightforward, particularly when an infectious etiology can be identified. In the minority of presentations that represent new occurrences of the idiopathic inflammatory bowel diseases (IBD), making a positive diagnosis and, indeed, distinguishing between Crohn’s disease and ulcerative colitis are also routine matters. However, a casual diagnosis of IBD may result in critical errors in management in that incorrect diagnosis may result in inappropriate or even contraindicated treatment. The issue remains that no gold standard test exists for the diagnosis of IBD. For this reason, diagnosing Crohn’s disease and ulcerative colitis continues to be a more than occasional challenge to the practicing gastroenterologist. Until such time as highly specific and sensitive diagnostic tests for IBD are devised, distinguishing among various forms of intestinal inflammation of idiopathic and identifiable causes will remain a test of clinical acumen, drawing on relevant history, attentive physical examination, judicious laboratory testing, and detailed review of radiographic, endoscopic, and pathologic data. This article reviews the findings that are most helpful in distinguishing various forms of intestinal inflammation. The comments below are divided into 2 parts: first, a review of the points of history, physical examination, and laboratory data useful in correctly diagnosing patients who present with a clinical syndrome suggestive of IBD; and second, a summary of the features that help to differentiate among inflammatory conditions of the bowel, organized by clinical syndrome as presentations of ileitis, proctitis, colitis, and the difficult pouch.

85 DIFFERENTIAL GROWTH AND CLONALITY OF GUT T-CELLS AMONG CROHN'S DISEASE (CD), ULCERATIVE COLITIS (UC), UNDETERMINED INFLAMMATION (NON-IBD) AND CONTROL CHILDREN

T-cells are critical to intestinal immunoregulation. CD and UC are characterized by persistent T-cells infiltrates, suggesting that abnormal T-cell proliferation is involved in disease pathogenesis. We investigated growth, clonality and clonal size of mucosal T-cells from CD, UC, non-IBD and control children. Mucosal biopsies were obtained endoscopically from small or large bowel. T-cell lines (>90% CD4+, TCRαβ+) were established with IL-2 (20 U/ml), and subsequently cloned at 0.3 cells/well with allogeneic feeder cells. The number of T-cells in each culture was assessed at 2, 3 and 4 weeks; clonal efficiency and size were determined at 3 and 7 weeks, respectively. Results: 1) CD, non-IBD and control T-cells grew exponentially for 3 weeks, whereas UC cells started declining at 2 weeks. At 3 weeks the number of CD T-cells was significantly (*p<0.02) greater than that of non-IBD, control and UC cells. Non-IBD and control also grew significantly (**p<0.002) more than UC cells. Similar differences were also noted at 4 weeks. Table 2) Clonal efficiency of UC T-cells was significantly (p<0.03) lower than CD, non-IBD and control cells. 3) The size of UC clones was significantly (p<0.03) smaller than CD clones. Each type of gut inflammation appears to be associated with unique patterns of T-cell proliferation, regardless of duration and therapy. This points to distinct pathogenic mechanisms for CD, UC and non-IBD. Such difference may help distinguishing and managing patients with various forms of intestinal inflammation.

Inflammatory Bowel Disease

Inflammatory bowel disease in children encompasses at least two forms of intestinal inflammation: ulcerative colitis and Crohn's disease. These two disease processes are differentiated based on clinical presentation, radiologic findings, endoscopic findings, histologic evaluation, and exclusion of alternative causes. The treatment and operative interventions are reviewed.

Inflammatory bowel disease associated circulating immune complexes.

Circulating immune complexes have been detected in patients with inflammatory bowel disease (IBD). To determine if these complexes are related specificially to IBD or more generally to loss of intestinal mucosal integrity, we compared circulating immune complex levels in the sera of 86 IBD patients, nine pseudomembranous and nine bacterial colitis patients, and 42 healthy controls. Immune complexes were measured by a Raji cell radioimmunoassay. Raji detectable circulating immune complex levels were significantly higher in the IBD group than in the healthy controls (P<0.001). Circulating immune complex levels in the pseudomembranous-bacterial colitis group and the healthy controls were essentially identical. While nearly 20% of the IBD patients (16 of 86) had abnormally high levels, none of the patients with the other forms of intestinal inflammation (0 of 18) had abnormal levels. These data suggest that the circulating immune complexes present in inflammatory bowel disease patients are related to the IBD process rather than to non-specific mucosal cell (barrier) damage. Patients with intestinal inflammation and normal peripheral immune complex levels also had normal mesenteric vein levels. These data suggest that lack of formation, rather than more efficient hepatic reticuloendothelial clearance, was primarily responsible for the absence of detectable complexes in Raji negative individuals. Circulating immune complex levels did not correlate with type, location, severity, or extraintestinal manifestations of inflammatory bowel disease. The absence of Raji detectable circulating immune complexes in the majority of patients, even in those with extraintestinal manifestations, raises serious doubts about the pathogenic significance of such complexes. Nevertheless, as the circulating immune complexes appear to be disease related, they may be used to isolate and identify disease specific antigen(s) of possible aetiological importance.