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Severe Colitis (severe + colitis)
Selected AbstractsThe Management of Acute Severe Colitis: ACPGBI Position StatementCOLORECTAL DISEASE, Issue 2008S. R. Brown First page of article [source] Inhibition of NKG2D receptor function by antibody therapy attenuates transfer-induced colitis in SCID miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2007Stine Kjellev Dr. Abstract A role for the activating NK-receptor NKG2D has been indicated in several autoimmune diseases in humans and in animal models of type 1 diabetes and multiple sclerosis, and treatment with monoclonal antibodies to NKG2D attenuated disease severity in these models. In an adoptive transfer-induced model of colitis, we found a significantly higher frequency of CD4+NKG2D+ cells in blood, mesenteric lymph nodes, colon, and spleen from colitic mice compared to BALB/c donor-mice. We, therefore, wanted to study the effect of anti-NKG2D antibody (CX5) treatment initiated either before onset of colitis, when the colitis was mild, or when severe colitis was established. CX5 treatment decreased the detectable levels of cell-surface NKG2D and prophylactic administration of CX5 attenuated the development of colitis significantly, whereas a more moderate reduction in the severity of disease was observed after CX5 administration to mildly colitic animals. CX5 did not attenuate severe colitis. We conclude that the frequency of CD4+NKG2D+ cells increase during development of experimental colitis. NKG2D may play a role in the early stages of colitis in this model, since early administration of CX5 attenuated disease severity. [source] MHC class II-independent CD25+ CD4+ CD8,,,+ ,,, T cells attenuate CD4+ T cell-induced transfer colitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2004Tamara Krajina Abstract CD4+ ,,, T cell populations that develop in mice deficient in MHC class II (through ,knockout' of either the A,, or the A, chain of the I-Ab molecule) comprise a major ,single-positive' (SP) CD4+ CD8, subset (60,90%) and a minor ,double-positive' (DP) CD4+ CD8,,,+ subset (10,40%). Many DP T cells found in spleen, mesenteric lymph nodes (MLN) and colonic lamina propria (cLP) express CD25, CD103 and Foxp3. Adoptive transfer of SP but not DP T cells from A,,/, or A,,/, B6 mice into congenic RAG,/, hosts induces colitis. Transfer of SP T cells repopulates the host with only SP T cells; transfer of DP T cells repopulates the host with DP and SP T cells. Anti-CD25 antibody treatment of mice transplanted with DP T cells induces severe, lethal colitis; anti-CD25 antibody treatment of mice transplanted with SP T cells further aggravates the course of severe colitis. Hence, regulatory CD25+ T cells within (or developing from) the DP T cell population of MHC class II-deficient mice control the colitogenic potential of CD25, CD4+ T cells. [source] Cytomegalovirus in inflammatory bowel disease: Pathogen or innocent bystander?INFLAMMATORY BOWEL DISEASES, Issue 9 2010Garrett Lawlor MD Abstract The role of cytomegalovirus (CMV) in exacerbations of inflammatory bowel disease (IBD) remains a topic of ongoing debate. Current data are conflicting as to whether CMV worsens inflammation in those with severe colitis, or is merely a surrogate marker for severe disease. The interpretation of existing results is limited by mostly small, retrospective studies, with varying definitions of disease severity and CMV disease. CMV colitis is rare in patients with Crohn's disease or mild-moderate ulcerative colitis. In patients with severe and/or steroid-refractory ulcerative colitis, local reactivation of CMV can be detected in actively inflamed colonic tissue in about 30% of cases. Where comparisons between CMV+ and CMV, steroid-refractory patients can be made, most, but not all, studies show no difference in outcomes according to CMV status. Treatment with antiviral therapy has allowed some patients with severe colitis to avoid colectomy despite poor response to conventional IBD therapies. This article reviews the immunobiology of CMV disease, the evidence for CMV's role in disease severity, and discusses the outcomes with antiviral therapy. (Inflamm Bowel Dis 2010) [source] Activation of the cannabinoid 2 receptor (CB2) protects against experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 11 2009Martin A. Storr MD Abstract Background: Activation of cannabinoid (CB)1 receptors results in attenuation of experimental colitis. Our aim was to examine the role of CB2 receptors in experimental colitis using agonists (JWH133, AM1241) and an antagonist (AM630) in trinitrobenzene sulfonic acid (TNBS)-induced colitis in wildtype and CB2 receptor-deficient (CB mice. Methods: Mice were treated with TNBS to induce colitis and then given intraperitoneal injections of the CB2 receptor agonists JWH133, AM1241, or the CB2 receptor antagonist AM630. Additionally, CB mice were treated with TNBS and injected with JWH133 or AM1241. Animals were examined 3 days after the induction of colitis. The colons were removed for macroscopic and microscopic evaluation, as well as the determination of myeloperoxidase activity. Quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) for CB2 receptor was also performed in animals with TNBS and dextran sodium sulfate colitis. Results: Intracolonic installation of TNBS caused severe colitis. CB2 mRNA expression was significantly increased during the course of experimental colitis. Three-day treatment with JWH133 or AM1241 significantly reduced colitis; AM630 exacerbated colitis. The effect of JWH133 was abolished when animals were pretreated with AM630. Neither JWH133 nor AM1241 had effects in CB mice. Conclusions: We show that activation of the CB2 receptor protects against experimental colitis in mice. Increased expression of CB2 receptor mRNA and aggravation of colitis by AM630 suggests a role for this receptor in normally limiting the development of colitis. These results support the idea that the CB2 receptor may be a possible novel therapeutic target in inflammatory bowel disease. (Inflamm Bowel Dis 2009) [source] Early bacterial dependent induction of inducible nitric oxide synthase (iNOS) in epithelial cells upon transfer of CD45RBhigh CD4+ T cells in a model for experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 12 2007Gerard Dijkstra MD Abstract Background: Both the role of inducible nitric oxide synthase (iNOS) in the development of inflammatory bowel disease (IBD) as well as the molecular details governing its mucosal induction remain unclear. Methods: In the present study we evaluated the role of the residing intestinal microflora in the induction of epithelial iNOS upon transfer of CD45RBhigh CD4+ T cells to SCID mice. CB-17 SCID mice were reared with conventional flora (CNV) or germfree CB-17 SCID mice were monoassociated with Helicobacter muridarum, act A(,) mutant Listeria monocytogenes, segmented filamentous bacteria (SFB), or Ochrobactrum anthropi. Results: Within 2 weeks CNV SCID mice injected with CD45RBhigh CD4+ T cells showed a focal, epithelial iNOS expression on the apical site of villi that preceded the infiltration of CD4+ T cells and cytokine production followed by extension of this expression to the entire surface along the whole crypt axis as the colitis progressed. SCID mice monoassociated with H. muridarum developed a severe colitis and showed high epithelial iNOS expression. CNV-SCID mice without T cells and SCID mice monoassociated with SFB did not show any iNOS expression, whereas SCID mice monoassociated with act A(,) mutant L. monocytogenes and O. anthropi showed some scattered epithelial iNOS staining on the apical site of a few villi, but none of these mice developed colitis. Conclusions: These findings demonstrate that the expression of epithelial iNOS is highly bacterium-specific and correlates with the severity of disease, suggesting an important role for this enzyme in the development of IBD. (Inflamm Bowel Dis 2007) [source] Segmented filamentous bacteria in a defined bacterial cocktail induce intestinal inflammation in SCID mice reconstituted with CD45RBhigh CD4+ T cellsINFLAMMATORY BOWEL DISEASES, Issue 10 2007Renata Stepankova PhD Abstract Background: The aim was to analyze the influence of intestinal microbiota on the development of intestinal inflammation. We used the model of chronic inflammation that develops spontaneously in the colon of conventional severe combined immunodeficiency (SCID) mice restored with the CD45 RBhigh subset of CD4+T cells isolated from the spleen of normal BALB/c mice. Methods: A CD4+CD45RBhigh subpopulation of T cells was purified from the spleen of conventional BALB/c mice by magnetic separation (MACS) and transferred into immunodeficient SCID mice. Germ-free (GF) SCID mice or SCID mice monoassociated with Enterococcus faecalis, SFB (segmented filamentous bacteria), Fusobacterium mortiferum, Bacteroides distasonis, and in combination Fusobacterium mortiferum + SFB or Bacteroides distasonis + SFB were used as recipients. SCID mice were colonized by a defined cocktail of specific pathogen-free (SPF) bacteria. Mice were evaluated 8,12 weeks after the cell transfer for clinical and morphological signs of inflammatory bowel disease (IBD). Results: After the transfer of the CD4+CD45RBhigh T-cell subpopulation to SCID mice severe colitis was present in conventional animals and in mice colonized with a cocktail of SPF microflora plus SFB. Altered intestinal barrier in the terminal ileum of mice with severe colitis was documented by immunohistology using antibodies to ZO-1 (zona occludens). Conclusions: Only SFB bacteria together with a defined SPF mixture were effective in triggering intestinal inflammation in the model of IBD in reconstituted SCID mice, while no colitis was detected in GF mice or in mice colonized either with SPF microflora or monoassociated only with SFB or colonized by Bacteroides distasonis + SFB or Fusobacterium mortiferum + SFB. (Inflamm Bowel Dis 2007) [source] Role of NK1.1+ and AsGm-1+ cells in oral immunoregulation of experimental colitisINFLAMMATORY BOWEL DISEASES, Issue 2 2003Shivti Trop Abstract NK1.1 and AsGm-1 expressing cells play a role in immunomodulation. Our purpose was to determine the role of NK1.1+ and AsGm-1+ expressing cells in the inflammatory/tolerance paradigm in experimental colitis. Oral tolerance towards colitis-extracted proteins had previously been shown to alleviate experimental colitis. Colitis was induced in C57/B6 mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Oral tolerance was induced via five oral doses of proteins extracted from TNBS-colitis colonic wall. Clinical, macroscopic, and microscopic scores were used for colitis assessment. To evaluate the putative role of AsGm-1 in tolerance induction, depletion of AsGm-1 expressing cells was performed. To evaluate the mechanism of tolerance induction, liver-associated NKT lymphocytes were harvested 14 days following tolerance induction, and cultured with concanavalin A (con A) and colitis-extracted proteins. T cell subsets were measured by flow cytometry. Cytokine expression was measured by intracellular staining and enzyme-linked immunosorbent assay (ELISA). Orally tolerized mice exhibited significant alleviation of the clinical, macroscopic, and microscopic parameters of colitis, with increased CD4+IL4+/CD4+IFN,+ lymphocyte ratio, increased IL-4, and decreased IFN, and IL-12 serum levels. In contrast, orally fed mice that were AsGm-1 depleted showed evidence of severe colitis. These mice exhibited significant decreased CD4+IL4+/CD4+IFN,+ ratios, and an increase in IFN, and IL-12, with decreased IL-4 levels. NKT cells harvested from tolerized mice secreted high levels of antiinflammatory cytokines. In contrast, in nontolerized mice, NKT cells mainly secreted proinflammatory cytokines. In a tolerized environment, both NK1.1 and AsGm-1 expressing cells are essential for disease alleviation. In contrast, in a nontolerized environment, AsGm-1 expressing cells support an antiinflammatory immune paradigm, while NKT lymphocytes support a proinflammatory shift. [source] Delayed surgery for acute severe colitis is associated with increased risk of postoperative complications,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 3 2010J. Randall Background: This study determined the long-term outcome after colectomy for acute severe ulcerative colitis (ASUC) and assessed whether the duration of in-hospital medical therapy is related to postoperative outcome. Methods: All patients who underwent urgent colectomy and ileostomy for ASUC between 1994 and 2000 were identified from a prospective database. Patient details, preoperative therapy and complications to last follow-up were recorded. Results: Eighty patients were identified, who were treated with intravenous steroids for a median of 6 (range 1,22) days before surgery. Twenty-three (29 per cent) also received intravenous ciclosporin. There were 23 complications in 22 patients in the initial postoperative period. Sixty-eight patients underwent further planned surgery, including restorative ileal pouch,anal anastomosis in 57. During a median follow-up of 5·4 (range 0·5,9·0) years, 48 patients (60 per cent) developed at least one complication. Patients with a major complication at any time during follow-up had a significantly longer duration of medical therapy before colectomy than patients with no major complications (median 8 versus 5 days; P = 0·036). Conclusion: Delayed surgery for patients with ASUC who do not respond to medical therapy is associated with an increased risk of postoperative complications. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | ||||||||||