Portal de Periódicos da CAPES

New Concepts in the Pathophysiology of Inflammatory Bowel Disease

2005; American College of Physicians; Volume: 143; Issue: 12 Linguagem: Inglês

10.7326/0003-4819-143-12-200512200-00007

1539-3704

Giorgos Bamias, Mark R. Nyce, Sarah A. De La Rue, Fabio Cominelli,

Autoimmune and Inflammatory Disorders Research

Reviews20 December 2005New Concepts in the Pathophysiology of Inflammatory Bowel DiseaseGiorgos Bamias, MD, Mark R. Nyce, MD, Sarah A. De La Rue, PhD, and Fabio Cominelli, MD, PhDGiorgos Bamias, MDFrom University of Virginia, Charlottesville, Virginia., Mark R. Nyce, MDFrom University of Virginia, Charlottesville, Virginia., Sarah A. De La Rue, PhDFrom University of Virginia, Charlottesville, Virginia., and Fabio Cominelli, MD, PhDFrom University of Virginia, Charlottesville, Virginia.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-143-12-200512200-00007 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Clinical PrinciplesThe inflammatory bowel diseases (IBDs), that is, Crohn disease and ulcerative colitis, affect approximately 1 million persons in North America and several million persons worldwide.Approximately 30% of patients present between 10 and 30 years of age.Current therapeutic options are limited and include nonspecific anti-inflammatory and immunosuppresive medications.Surgery is required for 50% to 80% of patients with Crohn disease, while only 20% of patients with ulcerative colitis have surgery.Novel biological therapeutics have greatly improved the quality of life of patients with IBD.Pathophysiologic PrinciplesBoth genetic and environmental factors play important roles in disease pathogenesis.New hypotheses implicate the innate immune system and ...References1. Cominelli F. Cytokine-based therapies for Crohn's disease—new paradigms. N Engl J Med. 2004;351:2045-8. [PMID: 15537904] CrossrefMedlineGoogle Scholar2. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003;3:521-33. [PMID: 12876555] CrossrefMedlineGoogle Scholar3. Fiocchi C. Inflammatory bowel disease: etiology and pathogenesis. Gastroenterology. 1998;115:182-205. [PMID: 9649475] CrossrefMedlineGoogle Scholar4. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417-29. [PMID: 12167685] CrossrefMedlineGoogle Scholar5. Strober W, Fuss IJ, Blumberg RS. The immunology of mucosal models of inflammation. Annu Rev Immunol. 2002;20:495-549. [PMID: 11861611] CrossrefMedlineGoogle Scholar6. Pizarro TT, Arseneau KO, Bamias G, Cominelli F. Mouse models for the study of Crohn's disease. Trends Mol Med. 2003;9:218-22. [PMID: 12763527] CrossrefMedlineGoogle Scholar7. Fuss IJ, Boirivant M, Lacy B, Strober W. The interrelated roles of TGF-beta and IL-10 in the regulation of experimental colitis. J Immunol. 2002;168:900-8. [PMID: 11777988] CrossrefMedlineGoogle Scholar8. Strober W, Kelsall B, Fuss I, Marth T, Ludviksson B, Ehrhardt R, et al. Reciprocal IFN-gamma and TGF-beta responses regulate the occurrence of mucosal inflammation. Immunol Today. 1997;18:61-4. [PMID: 9057354] CrossrefMedlineGoogle Scholar9. Abreu MT, Arditi M. Innate immunity and toll-like receptors: clinical implications of basic science research. J Pediatr. 2004;144:421-9. [PMID: 15069387] CrossrefMedlineGoogle Scholar10. Reuter BK, Pizarro TT. Commentary: the role of the IL-18 system and other members of the IL-1R/TLR superfamily in innate mucosal immunity and the pathogenesis of inflammatory bowel disease: friend or foe? Eur J Immunol. 2004;34:2347-55. [PMID: 15307167] CrossrefMedlineGoogle Scholar11. Bonen DK, Cho JH. The genetics of inflammatory bowel disease. Gastroenterology. 2003;124:521-36. [PMID: 12557156] CrossrefMedlineGoogle Scholar12. Duerr RH. Update on the genetics of inflammatory bowel disease. J Clin Gastroenterol. 2003;37:358-67. [PMID: 14564181] CrossrefMedlineGoogle Scholar13. Ahmad T, Satsangi J, McGovern D, Bunce M, Jewell DP. Review article: the genetics of inflammatory bowel disease. Aliment Pharmacol Ther. 2001;15:731-48. [PMID: 11380312] CrossrefMedlineGoogle Scholar14. Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 1996;379:821-3. [PMID: 8587604] CrossrefMedlineGoogle Scholar15. Cavanaugh J. International collaboration provides convincing linkage replication in complex disease through analysis of a large pooled data set: Crohn disease and chromosome 16. Am J Hum Genet. 2001;68:1165-71. [PMID: 11309682] CrossrefMedlineGoogle Scholar16. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411:599-603. [PMID: 11385576] CrossrefMedlineGoogle Scholar17. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001;411:603-6. [PMID: 11385577] CrossrefMedlineGoogle Scholar18. Hampe J, Cuthbert A, Croucher PJ, Mirza MM, Mascheretti S, Fisher S, et al. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet. 2001;357:1925-8. [PMID: 11425413] CrossrefMedlineGoogle Scholar19. Cuthbert AP, Fisher SA, Mirza MM, King K, Hampe J, Croucher PJ, et al. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology. 2002;122:867-74. [PMID: 11910337] CrossrefMedlineGoogle Scholar20. Eckmann L, Karin M. NOD2 and Crohn's disease: loss or gain of function? Immunity. 2005;22:661-7. [PMID: 15963781] CrossrefMedlineGoogle Scholar21. Bevins CL. The Paneth cell and the innate immune response. Curr Opin Gastroenterol. 2004;20:572-80. [PMID: 15703685] CrossrefMedlineGoogle Scholar22. Yu Y, Sitaraman S, Gewirtz AT. Intestinal epithelial cell regulation of mucosal inflammation. Immunol Res. 2004;29:55-68. [PMID: 15181270] CrossrefMedlineGoogle Scholar23. Panwala CM, Jones JC, Viney JL. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J Immunol. 1998;161:5733-44. [PMID: 9820555] MedlineGoogle Scholar24. Hermiston ML, Gordon JI. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Science. 1995;270:1203-7. [PMID: 7502046] CrossrefMedlineGoogle Scholar25. Mennechet FJ, Kasper LH, Rachinel N, Li W, Vandewalle A, Buzoni-Gatel D. Lamina propria CD4+ T lymphocytes synergize with murine intestinal epithelial cells to enhance proinflammatory response against an intracellular pathogen. J Immunol. 2002;168:2988-96. [PMID: 11884471] CrossrefMedlineGoogle Scholar26. Kwon JH, Keates S, Bassani L, Mayer LF, Keates AC. Colonic epithelial cells are a major site of macrophage inflammatory protein 3alpha (MIP-3alpha) production in normal colon and inflammatory bowel disease. Gut. 2002;51:818-26. [PMID: 12427784] CrossrefMedlineGoogle Scholar27. Stadnyk AW. Intestinal epithelial cells as a source of inflammatory cytokines and chemokines. Can J Gastroenterol. 2002;16:241-6. [PMID: 11981577] CrossrefMedlineGoogle Scholar28. Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157:1261-70. [PMID: 8757634] MedlineGoogle Scholar29. Gor DO, Rose NR, Greenspan NS. TH1-TH2: a procrustean paradigm. Nat Immunol. 2003;4:503-5. [PMID: 12774069] CrossrefMedlineGoogle Scholar30. Bullens DM, Kasran A, Thielemans K, Bakkus M, Ceuppens JL. CD40L-induced IL-12 production is further enhanced by the Th2 cytokines IL-4 and IL-13. Scand J Immunol. 2001;53:455-63. [PMID: 11309153] CrossrefMedlineGoogle Scholar31. Fort M, Lesley R, Davidson N, Menon S, Brombacher F, Leach M, et al. IL-4 exacerbates disease in a Th1 cell transfer model of colitis. J Immunol. 2001;166:2793-800. [PMID: 11160346] CrossrefMedlineGoogle Scholar32. Garside P. Cytokines in experimental colitis [Editorial]. Clin Exp Immunol. 1999;118:337-9. [PMID: 10594548] CrossrefMedlineGoogle Scholar33. O'Shea JJ, Ma A, Lipsky P. Cytokines and autoimmunity. Nat Rev Immunol. 2002;2:37-45. [PMID: 11905836] CrossrefMedlineGoogle Scholar34. Pedotti R, De Voss JJ, Steinman L, Galli SJ. Involvement of both "allergic" and "autoimmune" mechanisms in EAE, MS and other autoimmune diseases. Trends Immunol. 2003;24:479-84. [PMID: 12967671] CrossrefMedlineGoogle Scholar35. Fedorak RN, Gangl A, Elson CO, Rutgeerts P, Schreiber S, Wild G, et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology. 2000;119:1473-82. [PMID: 11113068] CrossrefMedlineGoogle Scholar36. Schreiber S, Fedorak RN, Nielsen OH, Wild G, Williams CN, Nikolaus S, et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Crohn's Disease IL-10 Cooperative Study Group. Gastroenterology. 2000;119:1461-72. [PMID: 11113067] CrossrefMedlineGoogle Scholar37. Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group. N Engl J Med. 1997;337:1029-35. [PMID: 9321530] CrossrefMedlineGoogle Scholar38. Armuzzi A, De Pascalis B, Lupascu A, Fedeli P, Leo D, Mentella MC, et al. Infliximab in the treatment of steroid-dependent ulcerative colitis. Eur Rev Med Pharmacol Sci. 2004;8:231-3. [PMID: 15638236] MedlineGoogle Scholar39. Eidelwein AP, Cuffari C, Abadom V, Oliva-Hemker M. Infliximab efficacy in pediatric ulcerative colitis. Inflamm Bowel Dis. 2005;11:213-8. [PMID: 15735427] CrossrefMedlineGoogle Scholar40. Kohn A, Prantera C, Pera A, Cosintino R, Sostegni R, Daperno M. Infliximab in the treatment of severe ulcerative colitis: a follow-up study. Eur Rev Med Pharmacol Sci. 2004;8:235-7. [PMID: 15638237] MedlineGoogle Scholar41. Tsukada Y, Nakamura T, Iimura M, Iizuka BE, Hayashi N. Cytokine profile in colonic mucosa of ulcerative colitis correlates with disease activity and response to granulocytapheresis. Am J Gastroenterol. 2002;97:2820-8. [PMID: 12425554] CrossrefMedlineGoogle Scholar42. Becher B, Durell BG, Noelle RJ. IL-23 produced by CNS-resident cells controls T cell encephalitogenicity during the effector phase of experimental autoimmune encephalomyelitis. J Clin Invest. 2003;112:1186-91. [PMID: 14561703] CrossrefMedlineGoogle Scholar43. Becker C, Wirtz S, Blessing M, Pirhonen J, Strand D, Bechthold O, et al. Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. J Clin Invest. 2003;112:693-706. [PMID: 12952918] CrossrefMedlineGoogle Scholar44. Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12. Immunity. 2000;13:715-25. [PMID: 11114383] CrossrefMedlineGoogle Scholar45. Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, et al. IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity. 2002;16:779-90. [PMID: 12121660] CrossrefMedlineGoogle Scholar46. Bamias G, Martin C, Marini M, Hoang S, Mishina M, Ross WG, et al. Expression, localization, and functional activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J Immunol. 2003;171:4868-74. [PMID: 14568967] CrossrefMedlineGoogle Scholar47. Prehn JL, Mehdizadeh S, Landers CJ, Luo X, Cha SC, Wei P, et al. Potential role for TL1A, the new TNF-family member and potent costimulator of IFN-gamma, in mucosal inflammation. Clin Immunol. 2004;112:66-77. [PMID: 15207783] CrossrefMedlineGoogle Scholar48. Pelletier M, Bouchard A, Girard D. In vivo and in vitro roles of IL-21 in inflammation. J Immunol. 2004;173:7521-30. [PMID: 15585879] CrossrefMedlineGoogle Scholar49. Mehta DS, Wurster AL, Grusby MJ. Biology of IL-21 and the IL-21 receptor. Immunol Rev. 2004;202:84-95. [PMID: 15546387] CrossrefMedlineGoogle Scholar50. Kosiewicz MM, Nast CC, Krishnan A, Rivera-Nieves J, Moskaluk CA, Matsumoto S, et al. Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease. J Clin Invest. 2001;107:695-702. [PMID: 11254669] CrossrefMedlineGoogle Scholar51. Rivera-Nieves J, Bamias G, Vidrich A, Marini M, Pizarro TT, McDuffie MJ, et al. Emergence of perianal fistulizing disease in the SAMP1/YitFc mouse, a spontaneous model of chronic ileitis. Gastroenterology. 2003;124:972-82. [PMID: 12671894] CrossrefMedlineGoogle Scholar52. Bamias G, Martin C, Mishina M, Ross WG, Rivera-Nieves J, Marini M, et al. Proinflammatory effects of TH2 cytokines in a murine model of chronic small intestinal inflammation. Gastroenterology. 2005;128:654-66. [PMID: 15765401] CrossrefMedlineGoogle Scholar53. Rivera-Nieves J, Olson T, Bamias G, Bruce A, Solga M, Knight RF, et al. L-selectin, alpha 4 beta 1, and alpha 4 beta 7 integrins participate in CD4+ T cell recruitment to chronically inflamed small intestine. J Immunol. 2005;174:2343-52. [PMID: 15699171] CrossrefMedlineGoogle Scholar54. Desreumaux P, Brandt E, Gambiez L, Emilie D, Geboes K, Klein O, et al. Distinct cytokine patterns in early and chronic ileal lesions of Crohn's disease. Gastroenterology. 1997;113:118-26. [PMID: 9207269] CrossrefMedlineGoogle Scholar55. Markowitz J, Grancher K, Kohn N, Lesser M, Daum F. A multicenter trial of 6-mercaptopurine and prednisone in children with newly diagnosed Crohn's disease. Gastroenterology. 2000;119:895-902. [PMID: 11040176] CrossrefMedlineGoogle Scholar56. Kugathasan S, Werlin SL, Martinez A, Rivera MT, Heikenen JB, Binion DG. Prolonged duration of response to infliximab in early but not late pediatric Crohn's disease. Am J Gastroenterol. 2000;95:3189-94. [PMID: 11095340] CrossrefMedlineGoogle Scholar57. Danese S, Sans M, Fiocchi C. Inflammatory bowel disease: the role of environmental factors. Autoimmun Rev. 2004;3:394-400. [PMID: 15288007] CrossrefMedlineGoogle Scholar58. Linskens RK, Huijsdens XW, Savelkoul PH, Vandenbroucke-Grauls CM, Meuwissen SG. The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scand J Gastroenterol Suppl. 2001;:29-40. [PMID: 11768558] CrossrefMedlineGoogle Scholar59. Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology. 2004;126:1620-33. [PMID: 15168372] CrossrefMedlineGoogle Scholar60. Lodes MJ, Cong Y, Elson CO, Mohamath R, Landers CJ, Targan SR, et al. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest. 2004;113:1296-306. [PMID: 15124021] CrossrefMedlineGoogle Scholar61. Sutton CL, Kim J, Yamane A, Dalwadi H, Wei B, Landers C, et al. Identification of a novel bacterial sequence associated with Crohn's disease. Gastroenterology. 2000;119:23-31. [PMID: 10889151] CrossrefMedlineGoogle Scholar62. Mow WS, Vasiliauskas EA, Lin YC, Fleshner PR, Papadakis KA, Taylor KD, et al. Association of antibody responses to microbial antigens and complications of small bowel Crohn's disease. Gastroenterology. 2004;126:414-24. [PMID: 14762777] CrossrefMedlineGoogle Scholar63. Arnott ID, Landers CJ, Nimmo EJ, Drummond HE, Smith BK, Targan SR, et al. Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype. Am J Gastroenterol. 2004;99:2376-84. [PMID: 15571586] CrossrefMedlineGoogle Scholar64. Mow WS, Landers CJ, Steinhart AH, Feagan BG, Croitoru K, Seidman E, et al. High-level serum antibodies to bacterial antigens are associated with antibiotic-induced clinical remission in Crohn's disease: a pilot study. Dig Dis Sci. 2004;49:1280-6. [PMID: 15387358] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From University of Virginia, Charlottesville, Virginia.Acknowledgments: The authors thank the entire personnel of the Digestive Health Center of Excellence at the University of Virginia.Grant Support: By the United States Public Health Service/National Institutes of Health grants DK-42195, DK-44540, and DK-55812 to Fabio Cominelli and The UVa Digestive Health Research Center (P30 DK-67629).Disclosures: Honoraria: F. Cominelli (UCB Pharmaceuticals, Inc., Centocor, Elan, Sigma-Tau).Corresponding Author: Fabio Cominelli, MD, PhD, Division of Gastroenterology and Hepatology, P.O. Box 800708, University of Virginia Health System, Charlottesville, VA 22908; e-mail, [email protected]edu.Current Author Addresses: Drs. Bamias, Nyce, De La Rue, and Cominelli: Digestive Health Center of Excellence, University of Virginia, P.O. Box 800708, Charlottesville, VA 22908-0708. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByAssociation between IL-10 rs3024505 and susceptibility to inflammatory bowel disease: A systematic review and meta-analysisSystems biology approach highlights mechanistic differences between Crohn's disease and ulcerative colitisCircadian Clock Disruption Suppresses PDL1+ Intraepithelial B Cells in Experimental Colitis and Colitis-Associated Colorectal CancerExploring the Early Phase of Crohn's DiseaseRevisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural ProductsDetermination of the Intestinal Microbiome Composition in Patients with Crohn's Disease and Ulcerative Colitis of Different Age Categories and SexA panoramic review of IL-6: Structure, pathophysiological roles and inhibitorsImpairment of electroneutral Na + transport and associated downregulation of NHE3 contributes to the development of diarrhea following in vivo challenge with Brachyspira spp.The Potential of Mesenchymal Stem Cells to Treat Systemic Inflammation in HorsesNutrition and autoimmune diseasesA Comprehensive Review and Update on the Pathogenesis of Inflammatory Bowel DiseaseDisable to enable: morbidity and quality-of-life challenges in adolescents with Crohn's diseaseDeath-Domain-Receptor 3 Deletion Normalizes Inflammatory Gene Expression and Prevents Ileitis in Experimental Crohn's DiseaseHealthcare utilisation prior to the diagnosis of inflammatory bowel diseases and the influence of livestock exposure: A longitudinal case-control studyDiscovery and preliminary SAR of 14-aryloxy-andrographolide derivatives as antibacterial agents with immunosuppressant activityRelationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantationGut Barrier: Adaptive ImmunitySafety and Efficacy of Biologic Agents for the Management of Inflammatory Bowel Disease After Liver TransplantationThe potential role of fecal microbiota transplantation in the treatment of inflammatory Bowel diseaseTrudności w ustaleniu etiologii zmian płucnych u 15-letniej dziewczynki z wrzodziejącym zapaleniem jelita grubegoMouse models of inflammatory bowel disease for investigating mucosal immunity in the intestineOral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in AthletesRecent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel DiseaseIntestinal anti-inflammatory effects of Passiflora edulis peel in the dextran sodium sulphate model of mouse colitisA Novel Role for TL1A/DR3 in Protection against Intestinal Injury and InfectionA mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel diseaseNeuroimmune Modulation of Gut FunctionPrebiotics and Probiotics in Inflammatory Bowel Disease (IBD)Pathway-based approaches to the treatment of inflammatory bowel diseaseOxidative Stress and DNA DamageClinical Features of Interleukin 10 Receptor Gene Mutations in Children With Very Early–Onset Inflammatory Bowel DiseaseCirculating Ghrelin Levels and Obestatin/Ghrelin Ratio as a Marker of Activity in Ulcerative ColitisCytokine profile in children with inflammatory bowel diseaseOf worms, mice and man: An overview of experimental and clinical helminth-based therapy for inflammatory bowel diseasePreliminary Results of the Influence of the In Vivo Use of a Lymphatic Dye (Patent Blue V) in the Surgical Treatment of Crohn's DiseaseInflammatory bowel disease pathogenesisDrug delivery strategies in the therapy of inflammatory bowel diseaseDiseases with Long-Term Consequences in Search of a Microbial AgentThe Commensal Bacterium Faecalibacterium prausnitzii Is Protective in DNBS-induced Chronic Moderate and Severe Colitis ModelsBronchiolitis in a Patient with Ulcerative Colitis Treated with ErythromycinIntestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel diseaseInteractions between the intestinal microbiota and innate lymphoid cellsDifferentiation between active and chronic Crohn's disease using MRI small-bowel motility examinations — Initial experienceImpact of probiotics on colonic microflora in patients with colitis: A prospective double blind randomised crossover studyComparative Study of Candidate Housekeeping Genes for Quantification of Target Gene Messenger RNA Expression by Real-Time PCR in Patients with Inflammatory Bowel DiseaseRole of commensal and probiotic bacteria in human health: a focus on inflammatory bowel diseaseThe tumor necrosis factor-like cytokine 1A/death receptor 3 cytokine system in intestinal inflammationIntestinal-Specific TNFα Overexpression Induces Crohn's-Like Ileitis in MiceAssociation of Inflammatory Bowel Disease With Familial Mediterranean Fever in Turkish ChildrenMicroarray analyses of peripheral whole blood cells from ulcerative colitis patients: Effects of leukocytapheresisRola terapii biologicznej w podtrzymaniu remisji u dzieci z chorobą Leśniowskiego i CrohnaThe mRNA level of the transforming growth factor β1 gene, but not the amount of the gene product, can be considered as a potential prognostic parameter in inflammatory bowel diseases in childrenProbiotics in inflammatory bowel disease: Pathophysiological background and clinical applicationsRole of LFA-1 in the activation and trafficking of T cells: Implications in the induction of chronic colitisProbiotics for the Treatment of Inflammatory Bowel DiseaseHematopoietic stem cell transplantation for curing children with severe autoimmune diseases: Is this a valid option?SOCS3 in immune regulation of inflammatory bowel disease and inflammatory bowel disease-related cancerAluminum as an adjuvant in Crohn's disease inductionRecruitment of Inflammatory and Immune Cells in the GutSAMP1/YitFc mouse strain: A spontaneous model of Crohn's disease-like ileitisIn Vitro Fermentation of Sugar Beet Arabino-Oligosaccharides by Fecal Microbiota Obtained from Patients with Ulcerative Colitis To Selectively Stimulate the Growth of Bifidobacterium spp. and Lactobacillus sppGp91 phox contributes to the development of experimental inflammatory bowel diseaseNaOH-Induced Crohn's Colitis in Rats: A Novel Experimental ModelChemokine Receptors in Inflammatory DiseasesAssessing Response and Loss of Response to Biological Therapies in IBDRole of the gut-associated and secondary lymphoid tissue in the induction of chronic colitisNew Paradigms in the Pathogenesis of IBDDifferential immune and genetic responses in rat models of Crohn's colitis and ulcerative colitisDo probiotic preparations for humans really have efficacy?Autologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-upPregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cellsHigh intestinal and systemic levels of decoy receptor 3 (DcR3) and its ligand TL1A in active ulcerative colitisFood-derived bioactives as potential regulators of the IL-12/IL-23 pathway implicated in inflammatory bowel diseasesImmune regulation of epithelial cell function: Implications for GI pathologiesProbiotics promote gut health through stimulation of epithelial innate immunityPrebiotics and Probiotics in Experimental Models of Rodent ColitisFrequency of single nucleotide polymorphisms in NOD1gene of ulcerative colitis patients: a case-control study in the Indian populationEtiología multifactorial y parcelas patogénicas de la enfermedad inflamatoria intestinalIL-7 is essential for lymphopenia-driven turnover of colitogenic CD4 + memory T cells in chronic colitisTargeted therapy to the IL-2R using diphtheria toxin and caspase-3 fusion proteins modulates Treg and ameliorates inflammatory colitisContraataque a la enfermedad intestinal inflamatoriaThe serum D-xylose test as a useful tool to identify malabsorption in rats with antigen specific gut inflammatory reactionPrebiotics in Chronic Intestinal InflammationPediatric Inflammatory Bowel Diseases and the Risk of Lymphoma: Should We Revise Our Treatment Strategies?Part 2-PrebioticsProinflammatory cytokines and receptor activator of nuclear factor κB-ligand/osteoprotegerin associated with bone deterioration in patients with Crohn's diseaseCancer antigen 125 levels in inflammatory bowel diseasesThe Epidemiology and Pathogenesis of Neoplasia in the Small IntestineTNFα blockade prevents the development of inflammatory bowel disease in HLA-B27 transgenic ratsSerum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inflammatory bowel diseaseFTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrowFight back against inflammatory bowel diseaseIonizing radiation-induced gene modulations, cytokine content changes and telomere shortening in mouse fetuses exhibiting forelimb defectsLes marqueurs sérologiques des maladies inflammatoires chroniques intestinales (MICI)Crohn's disease: beyond antagonists of tumour necrosis factorTreatment of Inflammatory Bowel Disease: A Role for Hypnotherapy?Immunosenescent colitogenic CD4+ T cells convert to regulatory cells and suppress colitisNeuro-immune interactions in inflammatory bowel disease and irritable bowel syndrome: Future therapeutic targetsMyD88-Dependent Pathway in T Cells Directly Modulates the Expansion of Colitogenic CD4 + T Cells in Chronic ColitisMucosal NOD2 expression and NF-κB activation in pediatric Crohn's diseaseAnti–α-enolase Antibodies in Patients with Inflammatory Bowel DiseaseVulvar UlcersOpposing Regulation of the Tight Junction Protein Claudin-2 by Interferon-γ and Interleukin-4Blockade of NKG2D signaling prevents the development of murine CD4 + T cell-mediated colitisEpidermal growth factor stimulates Rac activation through Src and phosphatidylinositol 3-kinase to promote colonic epithelial cell migrationSystemic, but Not Intestinal, IL-7 Is Essential for the Persistence of Chronic ColitisInnate and adaptive immune responses related to IBD pathogenesisResistin-Like Molecule β (RELMβ/FIZZ2) Is Highly Expressed in the Ileum of SAMP1/YitFc Mice and Is Associated with Initiation of IleitisMast cells and nerves tickle in the tummyNatalizumab: pharmacology, clinical efficacy and safety in the treatment of patients with Crohn's diseaseThe Immune Response in Inflammatory Bowel DiseaseLate-breaking news from the "4th International Meeting on Inflammatory Bowel Diseases" Capri, 2006NV-52Induction of experimental acute ulcerative colitis in rats by administration of dextran sulfate sodium at low concentration followed by intracolonic administration of 30% ethanolEfficacy of infliximab for luminal and fistulizing Crohn's disease and in ulcerative colitisImmunopathogenesis of inflammatory bowel disease: current conceptsMode of function of biological anti-TNF agents in the treatment of inflammatory bowel diseasesMaladie de Crohn et génétique: connaissances actuellesImmunologic and Molecular Mechanisms in Inflammatory Bowel DiseaseCytokine Therapy for Crohn's Disease: Advances in Translational ResearchThoracic Manifestations of Inflammatory Bowel DiseasePeau et affections du tube digestifPiel y afecciones del tubo digestivoHeparanase upregulation by colonic epithelium in inflammatory bowel diseaseMechanisms underlying inflammatory bowel diseaseCrohn's disease: The cost of comfortable inactionClinical trials reportNovel Therapies for Crohn's Disease: Focus on Immunomodulators and AntibioticsEvidence-based medications for the treatment of the inflammatory bowel diseasesDrug Insight: antagonists of tumor-necrosis factor-α in the treatment of inflammatory bowel diseaseDirections for Basic ScienceAdvances in GI Pharmacology and Therapeutics 20 December 2005Volume 143, Issue 12Page: 895-904KeywordsAntigensCellsCrohn's diseaseCytokinesGenetic diseasesInflammatory bowel diseaseInnate immune systemPathogenesisUlcerative colitis ePublished: 20 December 2005 Issue Published: 20 December 2005 CopyrightCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...