Inflammatory bowel disease: New insights into pathogenesis and treatment

Journal of Internal Medicine

Volumn 252, Issue 6, 2002, Pages 475-496

  Ardizzone, S ^a   Bianchi Porro, Gabriele ^a,b  

^a UNIVERSITY OF MILAN   (Italy)

^b FATEBENEFRATELLI HOSPITAL   (Italy)

Author keywords

Crohn's disease; Pathogenesis; Therapy; Ulcerative colitis

Indexed keywords

AZATHIOPRINE; CASPASE RECRUITMENT DOMAIN PROTEIN 15; CD11 ANTIGEN; CD19 ANTIGEN; CD4 ANTIGEN; CIPROFLOXACIN; ETANERCEPT; GAMMA INTERFERON; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; INTEGRIN; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 11; INTERLEUKIN 12; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 4 RECEPTOR; INTERLEUKIN 6; LEUKOSIALIN; MERCAPTOPURINE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEIN; PROTEIN NOD1; PROTEIN P75; RIFAXIMIN; TACROLIMUS; TOLL LIKE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; UNCLASSIFIED DRUG; UNINDEXED DRUG;

CLINICAL TRIAL; CROHN DISEASE; CYTOKINE RELEASE; DISEASE COURSE; DISEASE PREDISPOSITION; DRUG EFFICACY; ENVIRONMENTAL FACTOR; GENE THERAPY; GENETIC SUSCEPTIBILITY; HEREDITY; HUMAN; IMMUNE SYSTEM; IMMUNOGENETICS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; TH1 CELL; TH2 CELL; TREATMENT OUTCOME; ULCERATIVE COLITIS;

BIOLOGICAL THERAPY; COLITIS, ULCERATIVE; CROHN DISEASE; ENVIRONMENTAL HEALTH; GENE THERAPY; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMMUNE SYSTEM DISEASES; INFECTION;

EID: 0036457057     PISSN: 09546820     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2796.2002.01067.x     Document Type: Review

References (182)

1. Ferguson A. Ulcerative colitis and Crohn's disease: Important and disabling diseases, still under-researched. BMJ 1994; 309: 355-6.
2. Ardizzone S, Bollani S, Manzionna G, Bianchi Porro G. Inflammatory bowel disease approaching the 3rd millennium: Pathogenesis and therapeutic implications? Eur J Gastroenterol Hepatol 1999; 11: 27-32.
3. Fiocchi C. Inflammatory bowel disease: Etiology and pathogenesis. Gastroenterology 1998; 115: 182-205.
4. Sands BE. Therapy of inflammatory bowel disease. Gastroenterology 2000; 118: S68-S82.
5. Shanahan F. Inflammatory bowel disease: Immunodiagnostics, immunotherapeutics and ecotherapeutics. Gastroenterology 2001; 120: 622-35.
6. Hugot JP, Chamaillard M, Zouali H et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001; 411: 599-603.
7. Ogura Y, Bonen DK, Inohara N et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 2001; 411: 603-6.
8. van Heel DA, McGovern DPB, Jewell DP. Crohn's disease: Genetic susceptibility, bacteria, and innate immunity. Lancet 2001; 357: 1902-4.
9. Mahida YR, Johal S. NF-kB may determine whether epithelial cell-microbial interactions in the intestine are hostile or friendly. Clin Exp Immunol 2001; 123: 347-9.
10. Beutler B. Autoimmunity and apoptosis: The Crohn's connection. Immunity 2001; 15: 5-14.
11. Jobin C, Sartor RB. NF-kB signalling protein as therapeutic targets for inflammatory bowel disease. Inflamm Bowel Dis 2000; 6: 206-13.
12. Ahmad T, Armuzzi A, Bunce M et al. The molecular classification of the clinical manifestations of Crohn'as disease. Gastroenterology 2002; 122: 854-66.
13. Cuthbert AP, Fisher SA, Mirza MM et al. The contribution of NOD2 gene mutations to the risk and site of disease in inflammatory bowel disease. Gastroenterology 2002; 122: 867-74.
14. Ahmad T, Satsangi J, Mcgovern D, Bunce M, Lewell DP. Review article. The genetics of inflammatory bowel disease. Aliment Pharmacol Therap 2001; 15: 731-48.
15. Satsangi J, Welsh KI, Bunce M. Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet 1996; 347: 1212-7.
16. Satsangi J, Parkes M, Louis E. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet 1996; 14: 199-202.
17. Futami S, Aoyama N, Honsako Y. HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression. Dig Dis Sci 1995; 40: 814-8.
18. Roussomousstakaki M, Satsangi J, Welsh K. Genetic markers may predict disease behavior in patients with ulcerative colitis. Gastroenterology 1997; 112: 1845-53.
19. Sandborn WJ, Landers CJ, Tremaine WJ, Targan SR. Association of antineutrophil cytoplasmic antibodies with resistance to treatment of left-sided ulcerative colitis: Results of a pilot study. Mayo Clin Proc 1996; 71: 431-6.
20. Farrell RJ, Murphy A, Long A. High multidrug resistance (P-glycopotein 170) expression in inflammatory bowel disease patients who failed medical therapy. Gastroenterology 2000; 118: 279-88.
21. Orchard TR, Thiyagaraja S, Welsh KI, Wordsworth BP, Hill Gaston JS, Jewell DP. Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 2000; 118: 274-8.
22. Kyo K, Parkes M, Takei Y. Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3. Hum Mol Genet 1999; 11: 413-20.
23. Papo M, Quer JC, Gutierrez C. Genetic heterogeneity within ulcerative colitis determined by an interleukin-1 receptor antagonist gene polymorphism and antineutrophil cytoplasmic antibodies. Eur J Gastroenterol Hepatol 1999; 118: 274-8.
24. Shanahan F. Crohn's disease. Lancet 2002; 359: 62-9.
25. Sartor RB. Enteric microflora in IBD: Pathogens or commensals? Inflamm Bowel Dis 1997; 3: 230-5.
26. Elliott DE, Urban JR Jr, Argo CK, Weinstock JV. Does the failure to acquire helmintic parasites predispose to Crohn's disease? FASEB J 2000; 4: 430-5.
27. Franceschi S, Panza E, La Vecchia C, Parazini F, Decarli A, Bianchi Porro G. Nonspecific inflammatory bowel disease and smoking. Am J Epidemiol 1987; 125: 445-52.
28. Lindberg E, Tysk C, Anderson K, Jarnerot G. Smoking and inflammatory bowel disease: A case control study. Gut 1988; 29: 352-7.
29. Cottone M, Rosselli M, Cammà C et al. Smoking habits and recurrence in Crohn's disease. Gastroenterology 1994; 106: 643-8.
30. Miller LG, Goldstein G, Murphy M, Ginns LC. Reversible alterations in immunoregulatrory T cells in smoking: Analysis by monoclonal antibodies and flow cytometry. Chest 1982; 82: 526-9.
31. Srivastava ED, Barton JR, O'Mahony S. Smoking, humoral immunity, and ulcerative colitis. Gut 1991; 32: 1016-9.
32. Cope GF, Heatley RV, Kelleher JK. Smoking and colonic mucus in ulcerative colitis. BMJ 1986; 293: 481.
33. Coulie B, Camilleri M, Bharucha AE, Sandborn WJ, Burton D. Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Aliment Pharmacol Ther 2001; 15: 653-63.
34. Madretsma S, Wolters LM, van Dijk JP. In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Eur J Gastroenterol Hepatol 1996; 8: 1017-20.
35. Hollander D, Vadheim C, Brettholz E, Pettersen GM, Delahunty T, Rotter JI. Increased intestinal permeability in patients with Crohn's disease and their relatives. Ann Intern Med 1986; 105: 883-5.
36. Evans JM, McMahon AD, Murray FE, McDevit DG, MacDonald TM. Non-steroidal anti-inflammatory drugs were associated with emergency admission to hospital for colitis due to inflammatory bowel disease. Gut 1997; 40: 619-22.
37. McCartney SA, Mitchell JA, Fairclough PD, Farthing MJ, Warner TD. Selective COX-2 inhibitors and human inflammatory bowel disease. Aliment Pharmacol Ther 1999; 13: 1115-7.
38. Theis MK, Boyko EJ. Patients perception of causes of inflammatory bowel disease. Am J Gastroenterol 1994; 89: 397-404.
39. Herbert TB, Cohen S. Stress and immunity in humans: A meta-analytic review. Psychosom Med 1993; 55: 364-79.
40. Levenstein S, Prantera C, Varvo V. Stress and exacerbation in ulcerative colitis: A prospective study of patients enrolled in remission. Am J Gastroenterol 2000; 95: 1213-20.
41. Madara JL, Podolsky DK, King NW, Sehagal PK, Moore R, Winter HS. Characterization of spontaneous colitis in cotton-top tamarins (Sanguinus oedipus) and its response to sulfasalazine. Gastroenterology 1985; 88: 13-9.
42. Maunder RG, Lancee WJ, Greenberg GR, Hunter JJ, Fernades BJ. Insecure attachment in a subgroup with ulcerative colitis defined by ANCA status. Dig Dis Sci 2000; 45: 2127-32.
43. Rutgeerts P, D'Haens G, Hicle M, Geboes K, Vantrappen G. Appendicectomy protects against ulcerative colitis. Gastroenterology 1994; 106: 1251-3.
44. Koutroubakis IE, Vlachonikolis IG. Appendicectomy and the development of ulcerative colitis: Results of a metanalysis of published case-control studies. Am J Gastroenterol 2000; 95: 171-6.
45. Anderson RE, Olaison G, Tysk C, Ekbom A. Appendicectomy and protection against ulcerative colitis. N Engl J Med 2001; 344: 808-14.
46. Fabia R, ArRajab A, Andersson M-L et al. Impairment of bacterial flora in human ulcerative colitis and experimental colits in the rat. Digestion 1993; 54: 248-55.
47. Sartor R. Microbial factors in the pathogenesis of Crohn's disease, ulcerative colitis, and experimental intestinal inflammation. In: Kirsner JB, eds. Inflammatory Bowel Disease, 5th Edn. Philadelphia: W.B. Saunders, 2000: 153-78.
48. Shanahan F. Probiotics and inflammatory bowel disease: Is there a scientific rationale? Inflamm Bowel Dis 2000; 6: 107-15.
49. Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol 1996; 4: 430-5.
50. Gordon JI, Hooper LV, McNevin SM, Wong M, Bry L. Epithelial cell growth and differentiation III. Promoting diversity in the intestine: Conversations between the microflora, epithelium and diffuse GALT. Am J Physiol 1997; 273: G565-G570.
51. Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Mayer zum Buschenfelde KH. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease. Clin Exp Immunol 1995; 102: 448-55.
52. Duchmann R, May E, Heike M, Knoille P, Neurath M, Meyer zum Buschenfelde KH. T cell specifity and cross reactivity towards enterobacteria, bacteroides, bifidobacterium, and antigens from resident intestinal flora in humans. Gut 1999; 44: 812-8.
53. Darfeuille-Michaud A, Neut C, Barnich N et al. Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease. Gastroenterology 1998; 115: 1405-13.
54. Swidsinski A, Ladhoff A, Pernthaler A et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 2002; 122: 4-54.
55. Elson CO. Commensal bacteria as targets in Crohn's disease. Gastroenterology 2000; 119: 254-7.
56. Fuss IJ, Neurath M, Boirivant M 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.
57. Farrell JR, Peppercorn MA. Ulcerative colitis. Lancet 2002; 359: 331-40.
58. Sartor RB. Pathogenesis and immune mechanisms of chronic inflammatory bowel diseases. Am J Gastroenterol 1997; 92(Suppl., December): S5-11.
59. Schuppan D, Hahn EG. MMPs in the gut: Inflammation hits the matrix. Gut 2000; 47: 12-4.
60. Heuschkel RB, MacDonald TT, Monteleone G, Bajaj-Elliott M, Walker Smith J, Pender SLF. Imbalance of stromolysin-1 and TIMP-1 in the mucosal lesions of children with inflammatory bowel disease. Gut 2000; 47: 57-62.
61. Pender SL, Tickle SP, Docherty AJ, Howie D, Wathen NC, MacDonald TT. A major role of matrix metalloproteinases in T cell injury in the gut. J Immunol 1997; 158: 1582-90.
62. Powrie F. T cells in inflammatory bowel disease: Protective and pathogenic roles. Immunity 1995; 3: 171-4.
63. Read S, Malmström V, Powrie F. Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that control intestinal inflammation. J Exp Med 2000; 192: 295-302.
64. Boirivant M, Marini M, Di Felice G et al. Lamina propria T cell in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis. Gastroenterology 1999; 116: 557-65.
65. Ina K, Itoh J, Fukushima K et al. Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. J Immunol 1999; 163: 1081-90.
66. Atreya R, Mudter J, Finotto S et al. Blockade of interleukin 6 transignalling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn's disease and experimental colitis in vivo. Nat Med 2000; 6: 583-8.
67. Boirivant M, Pica R, De Maria R, Testi R, Pallone F, Strober W. Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis. J Clin Invest 1996; 98: 2616-22.
68. Ueyama H, Kiyohara T, Sawada N et al. Fas ligand expression on lymphocytes in lesions of ulcerative colitis. Gut 1998; 43: 48-55.
69. Sands BE. Biological therapy for inflammatory bowel disease. Inflamm Bowel Dis 1997; 3: 95-113.
70. Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 1993; 75: 263-74.
71. Schreiber S, Heing T, Thiele HG, Raedler A. Immunoregulatory role of interleukin 10 in patients with inflammatory bowel disease. Gastroenterology 1995; 108: 1434-44.
72. Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 1995; 182: 1281-90.
73. MacDonald TT, Monteleone G. Interleukin-12 and Th1 immune responses in human Peyer's patches. Trends Immunol 2001; 22: 244-7.
74. Sartor RB. Cytokines in intestinal inflammation: Pathophysiological and clinical considerations. Gastroenterology 1994; 106: 533-9.
75. Amati L, Caradonna L, Jirillo E, Caccavo D. Immunological disorders in inflammatory bowel disease and immunotherapeutic implications. Ital J Gastroenterol Hepatol 1999; 31: 313-25.
76. Papadakis CA, Targan SA. Tumor necrosis factor: Biology and therapeutic inhibitors. Gastroenterology 2000; 119: 1148-57.
77. Blam ME, Stein RBS, Lichtenstein GR. Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease. Current and future perspectives. Am J Gastroenterol 2001; 96: 1977-97.
78. Lukacs NW, Chensue SW, Strieter RM, Warmington K, Kunkel SL. Inflammatory granuloma formation is mediated by TNF-alpha-inducible intercellular adhesion molecule-1. J Immunol 1994; 152: 5883-9.
79. Alexopulou L, Pasparikis M, Kollias G. A murine trans-membrane tumour necrosis factor (TNF) transgene induces arthritis by cooperative p55/p75 TNF recpetor signaling. Eur J Immunol 1997; 27: 2588-92.
80. van Deventer SJH. A place for TACE. Gut 2002; 51: 5-6.
81. Moss ML, Jin SL, Milla ME. Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 1997; 385: 733-5.
82. Black RA, Rauch CT, Kozlosky CJ. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 1997; 385: 729-33.
83. Brynskov J, Foegh P, Pedersen G et al. Tumour necrosis factor α converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Gut 2002; 51: 37-43.
84. Gordon MS, McCaskill-Stevens WJ, Battiato LA et al. A phase I trial of recombinant human interleukin-11 (neumega rhIl-11 growth factor) in women with breast cancer receiving chemotherapy. Blood 1996; 87: 3615-24.
85. Potten CS. Protection of the small intestine clonogenic stem cells from radiation-induced damage by pretreatment with interleukin 11 also increases murine survival time. Stem Cells 1996; 14: 452-9.
86. Qiu BS, Pfeiffer CJ, Keith JC Jr. Protection by recombinant human interleukin-11 against experimental TNB-induced colitis in rats. Dig Dis Sci 1996; 41: 1625-30.
87. Keith JC Jr, Albert LM, Ferranti TJ et al. Recombinant human interleukin-11 (rhIL-11) decreases inflammatory bowel disease in HLA-B27 transgenic rats (Abstract). Gastroenterology 1995; 108: A846.
88. Mangelsdorf DJ, Thummel C, Beato M. The nuclear receptor superfamily: The second decade. Cell 1995; 83: 835-9.
89. Fajas L, Auboeuf D, Raspe E. The organization, promoter analysis, and expression of the human PPArgamma gene. J Biol Chem 1997; 272: 19779-89.
90. Su CG, Wen X, Bailey ST. A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response. J Clin Invest 1999; 104: 383-9.
91. Dubuquoy L, Bourdon C, Peuchmaur M. Peroxisome proliferator-activated receptor (PPAR) gamma: A new target for the treatment of inflammtory bowel disease. Gastroenterol Clin Biol 2000; 24: 719-24.
92. Ardizzone S, Bianchi Porro G. The topical treatment of distal ulcerative colitis. Eur J Gastroenterol Hepatol 1996; 8: 599-602.
93. Ardizzone S, Molteni P, Bollani S, Bianchi Porro G. Guidelines for the treatment of ulcerative colitis in remission. Eur J Gastroenterol Hepatol 1997; 9: 836-41.
94. Ardizzone S, Bianchi Porro G. A practical guide to the management of distal ulcerative colitis. Drugs 1998; 55: 519-42.
95. Kirsner JB. 'Nonspecific' inflammatory bowel disease (ulcerative colitis and Crohn's disease) after 100 years-what next? Ital J Gastroenterol Hepatol 1999; 31: 651-8.
96. Prantera C, Scribano ML. Current treatment for prevention of relapse and recurence in Crohn's disease. Ital J Gastroenterol Hepatol 1999; 31: 519-20.
97. Su CG, Stein RB, Lewis JD, Lichtenstein GR. Azathioprine or 6-mercaptopurine for inflammatory bowel disease: Do risks outweigh benefits? Digest Liver Dis 2000; 32: 518-31.
98. Hanauer SB, Dassopoulos T. Evolving treatment strategies for inflammatory bowel disease. Ann Rev Med 2001; 52: 299-318.
99. Katz S. Update in medical therapy of ulcerative colitis. J Clin Gastroenterol 2002; 34: 397-407.
100. Dubinsky MC, Lamothe S, Yang HY et al. Pharmacogenomics and metabolite measurement of 6-mercaptopurine therapy in inflammatory bowel disease. Gastroenterology 2000; 118: 705-13.
101. Lennard L. TPMT in the treatment of Crohn's disease with azathioprine. Gut 2002; 51: 143-6.
102. Weinshilboum RN, Sladek SL. Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980; 32: 651-62.
103. Lennard L, van Loon JA, Weinshilboum RM. Pharmacogenetics of acute azathioprine toxicity: Relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989; 46: 149-54.
104. Ardizzone S, Samolvico F, Bollani S, Imbesi V, Colombo E, Bianchi Porro G. Azathioprine is more effective than oral 5-ASA in the treatment of steroid-dependent ulcerative colitis. Gastroenterology 2001; 120: A127.
105. Gormet JM, Lemann M, Cosnes J et al. Azathiprone (AZA) for ulcerative colitis: A retrospective multicenter study of 131 patients. Gastroenterology 2001; 120: A625.
106. Borody TJ, Leis S, Warren EF, Surace R. Treatment of severe Crohn's disease using antimycobacterium triple therapy - Approaching a cure? Digest Liver Dis 2002; 34: 29-38.
107. Shafran I, Kugler L, El-Zaatari FAK, Naser SA, Sandoval J. Open clinical trial of rifabutin and clarithromycine therapy in Crohn's disease. Digest Liver Dis 2002; 34: 22-8.
108. Turunen UM, Farkkila MA, Hakala K et al. Long-term treatment of ulcerative colitis with ciprofloxacin: A prospective, double-blind, placebo-controlled study. Gastroenterology 1998; 115: 1072-8.
109. Gionchetti P, Rizzello F, Ferrieri A et al. Rifaximin in patients with moderate or severe ulcerative colitis refractory to steroid-treatment: A double-blind, placebo-controlled trial. Dig Dis Sci 1999; 44: 1220-1.
110. Ledley FD. Somatic gene therapy in gastroenterology: Approaches and applications. J Pediatr Gastroenterol Nutr 1992; 14: 328-37.
111. Askari FK, McDonnell WM. Antisense-oligonucleotide therapy. N Engl J Med 1996; 334: 316-8.
112. Hogaboam CM, Vallance BA, Kumar A et al. Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease. J Clin Invest 1997; 100: 2766-76.
113. Deusch K, Mauthe B, Reiter C, Riethmuller G, Classen M. CD4-antibody treatment of inflammatory bowel disease: One year follow-up. Gastroenterology 1993; 104: A691.
114. Stronkhorst A, Radema S, Yong SL et al. CD4 antibody treatment in patients with active Crohn's disease: A phase I dose finding study. Gut 1997; 40: 320-7.
115. Emmrich J, Seyfarth M, Fleig WE, Emmrich F. Treatment of inflammatory bowel disease with anti-CD4 monoclonal antibody. Lancet 1991; 338: 570-1.
116. Emmrich J, Seyfarth M, Liebe S, Emmrich F. Anti-CD6 antibody treatment in inflammatory bowel disease without a long CD4+-cell depletion. Gastroenterology 1995; 108: A815.
117. Canva-Delcambre V, Jacquot S, Robinet E et al. Treatment of severe Crohn's disease with anti-CD4 monoclonal antibody. Aliment Pharmacol Ther 1996; 10: 721-7.
118. Schreiber S, Fedorak RN, Nielsen OH et al. Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn's disease. Gastroenterology 2000; 119: 1462-72.
119. Fedorak RN, Gangl A, Elson CO et al. Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. Gastroenterology 2000; 119: 1473-82.
120. Sands BE, Bank S, Sninsky CA et al. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease. Gastroenterology 1999; 117: 58-64.
121. Sands BE, Winston B, Salzberg B et al. A randomized, double-masked, placebo-controlled study of recombinat human interleukin leven (rhIL-11) in Crohn's disease subjects not receiving prednisone. Gastroenterology 1999; 116: A811.
122. Van Dullemen HM, van Deventer SJH, Hommes DW et al. Treatment of Crohn's disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2). Gastroenterology 1995; 109: 129-35.
123. McCabe RP, Woody J, van Deventer SJH et al. A multicenter trial of cA2 anti-TNF chimeric monoclonal antibody in patients with active Crohn's disease. Gastroenterology 1996; 110: A962.
124. Targan SR, Hanauer SB, van Deventer SJH et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor α for Crohn's disease. N Engl J Med 1997; 337: 1029-35.
125. Rutgeerts P, D'Haens G, Targan S et al. Efficacy and safety or retreatment with anti-tumor necrosis factor antibody (Infliximab) to maintain remission in Crohn's disease. Gastroenterology 1999; 117: 761-9.
126. Hanauer SB, Feagan BG, Lichtenstein GR et al. Maintenance Infliximab for Crohn's disease: The Accent I randomiased trial. Lancet 2002; 359: 1541-9.
127. D'Haens G, van Deventer S, van Hogezand R. Endoscopic and histological healing with infliximab anti-tumor necrosis factor antibodies in Crohn's disease: A European multicenter trial. Gastroenterology 1999; 116: 1029-34.
128. Present DH, Rutgeerts P, Targan S et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N Engl J Med 1999; 340: 1398-405.
129. Cohen RD, Tsang JF, Hanauer SB. Infliximab in Crohn's disease: First anniversary clinical experience. Am J Gastroenterol 2000; 95: 3469-77.
130. Farrell RJ, Shah SA, Lodhavia PJ et al. Clinical experience with infliximab therapy in 100 patients with Crohn's disease. Am J Gastroenterol 2000; 95: 3490-7.
131. Ricart E, Panaccione R, Loftus EV, Tremaine WJ, Sandborn WJ. Infliximab for Crohn's disease in clinical practice at the Mayo Clinic: The first 100 patients. Am J Gastroenterol 2001; 96: 722-9.
132. Arnott IDR, McDonald D, Williams A, Ghosh S. Clinical use of infliximab in Crohn's disease: The Edinburgh expereince. Aliment Pharmacol Ther 2001; 15: 1639-46.
133. Hommes DW, van de Heisteeg BH, van der Spek M, Bartelsman JFWM, van Deventer SJH. Infliximab treatment for Crohn's disease: One-year experience in a Dutch Academic Hospital. Inflamm Bowel Dis 2002; 8: 81-6.
134. Ardizzone S, Colombo E, Maconi G et al. Infliximab in treatment of Chron's disease: The Milan expierence. Digest Liver Dis 2002; 34: 411-8.
135. Stack WA, Mann SD, Roy AJ et al. Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn's disease. Lancet 1997; 349: 521-4.
136. Sandborn WJ, Hanauer SB, Katz S et al. Etanercept for active Crohn's disease: A randomised, double-blind, placebo-controlled trial. Gastroenterology 2001; 121: 1088-94.
137. Sands BE, Tremaine WJ, Sandborn WJ et al. Infliximab in the treatment of severe, steroid-refractory ulcerative colitis: A pilot study. Inflamm Bowel Dis 2001; 7: 83-8.
138. Chey WY, Hussain A, Ryan C, Potter GD, Shah A. Infliximab for refractory ulcerative coliis. Am J Gastroenterol 2001; 96: 2373-81.
139. Kyriakis JM, Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001; 81: 807-69.
140. Hommes D, Van Den Blink B, Plasse B et al. Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease. Gastroenterology 2002; 122: 7-14.
141. Yacyshyn BR, Bowen-Yacyshyn MB, Jewell L et al. A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease. Gastroenterology 1998; 114: 113-42.
142. Lewis JD, Lichtenstein GR, Stein RB et al. An open-label trial of the PPARγ lignad rosiglitazone for active ulcerative colitis. Am J Gastroenterol 2001; 96: 3323-8.
143. Sandborn WJ, Hanauer SB. Antitumor necrosis factor therapy for inflammatory bowel disease: A review of agents, pharmacology, clinical results, and safety. Inflamm Bowel Dis 1999; 5: 119-33.
144. Moreira AL, Sampaio EP, Zmuidzinas A, Frindt P, Smith KA, Kaplan G. Thalidomide exerts its inhibitory action on TNFα by enhancing mRNA degradation. J Exp Med 1993; 177: 1675-80.
145. Moller DR, Wysocka M, Greenlee BM et al. Inhibition of IL-12 production by thalidomide. J Immunol 1997; 159: 5157-61.
146. Ehrenpreis ED, Kane SV, Cohen LB, Cohem RD. Thalidomide therapy for patients with refractory Crohn's disease: An open-label trial. Gastroenterology 1999; 117: 1271-7.
147. Vasiliauskas EA, Kam LY, Abreu-Martin MT et al. An open-label pilot study of low-dose thalidomide in chronically active, steroid-dependent Crohn's disease. Gastroenterology 1999; 117: 1278-87.
148. Kam LY, Vasiliauskas EA, Abreu MT, Hassard PV, Zeldis J, Targan SR. Open label pilot study of thalidomide (THAL) as a novel therapyt for medically resistant ulcerative colitis. Gastroenterology 2000; 118: A582.
149. Hashimoto Y. Novel biological response modifiers derived from thalidomide. Cur Med Chem 1998; 5: 163-78.
150. Marriott JB, Westby M, Cookson S et al. CC-3052: A water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-alpha production. J Immunol 1998; 161: 4236-43.
151. The U.S. multicenter FK506 liver study group. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression in liver transplantation. N Engl J Med 1994; 331: 1110-5.
152. Flanagan WM, Corthesy B, Bram RJ, Crabtree GR. Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature 1991; 352: 803-7.
153. Sandborn WJ. Preliminary report on the use of oral tacrolimus (FK506) in the treatment of complicated proximal small bowel and fistulizing Crohn's disease. Am J Gastroenterol 1997; 92: 876-9.
154. Fellerman K, Ludwig D, Stahl M, David-Walek T, Stange EF. Steroid-unresponsive acute attacks of inflammatory bowel disease: Immunomodulation by tacrolimus (FK506). Am J Gastroenterol 1998; 93: 1860-6.
155. Lowry PW, Weaver AL, Tremaine WJ, Sandborn WJ. Combination therapy with oral tacrolimus (FK506) and azathiprine or 6-mercaptopurine for treatment-refractory Crohn's disease perianal fistulae. Inflamm Bowel Dis 1999; 5: 239-45.
156. Bousvaros A, Wang A, leichtner AM. Tacrolimus (FK506) treatment of fulminant colitis in a child. J Pediatr Gastroenterol Nutr 1996; 23: 329-33.
157. Sandborn WJ, Present DH, Isaacs KL et al. Tacrolimus (FK506) for the treatment of perianal and enterocutaneous fistulas in patients with Crohn's disease: A randomized, double-blind, placebo-controlled trial. Gastroenterology 2002; 122: A670.
158. Lipsky JJ. Mycophenolate mofetil. Lancet 1996; 348: 1357-9.
159. Allison AC, Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplant 1996; 10: 77-84.
160. Allison AC, Eugui EM. Immunosuppressive and other effects of mycophenolic acid and an ester prodrug, mycophenolate mofetil. Immunol Rev 1993; 136: 5-28.
161. Neurath MF, Wanitschke R, Peters M, Krummenauer F, Meyer zum Büschenfelde K-H, Schlaak JF. Randomised trial of mycophenolate mofetil versus azathioprine fro treatment of chronic active Crohn's disease. Gut 1999; 44: 625-8.
162. Neurath MF, Fuss I, Kelsall BL, Presky DH, Waegell W, Strober W. Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. J Exp Med 1996; 183: 2605-16.
163. Kreuis W, Schütz E, Fric P, Fixa B, Judmaier G, Stolte M. Double-blind comparison of an oral Escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 1997; 1: 853-8.
164. Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DMN, Axon ATR. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: A randomised trial. Lancet 1999; 354: 635-9.
165. Gionchetti P, Rizzello F, Venturi A et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology 2000; 119: 305-9.
166. Geboes K, Rutgeerts PJ. Vasculitis and Crohn's disease. Res Forums 1995; 17: 57-65.
167. Wakefield AJ, Sawyerr AFM, Dhillon AP et al. Pathogenesis of Crohn's disease: Multifocal gastrointestinal infarction. Lancet 1989; 2: 1057-62.
168. Talbot RW, Heppell J, Dozois RR, Beart RW Jr. Vascular complication of inflammatory bowel disease. Mayo Clin Proc 1986; 61: 140-5.
169. Gaffney PR, Doyle CT, Gaffney A, Hogan J, Hayes DP, Annis P. Paradoxical response to heparine in 10 patients with ulcerative colitis. Am J Gastroenterol 1995; 90: 220-3.
170. Evans RC, Shim Wong V, Morris AL, Rhodes JM. Treatment of corticosteroid-resistant ulcerative colitis with heparin: A report of 16 cases. Aliment Pharmacol Ther 1997; 11: 1037-40.
171. Panes J, Esteve M, Cabre E et al. Comparison of heparin and steroids in the treatment of moderate and severe ulcerative colitis. Gastroenterology 2000; 119: 903-8.
172. Ang YS, Mahmud N, White B et al. Randomized comparison of unfractioned heparin with corticosteroids in severe active inflammatory bowel disease. Aliment Pharmacol Ther 2000; 14: 1015-22.
173. Collins S. The immunomodulation of enteric neuromuscular function: Implication for motility and inflammatory disorders. Gastroenterology 1996; 111: 1683-99.
174. Ottaway CA, Stanisz AM. Neural-immune interactions in the intestine: Implications for inflammatory bowel disease. In: Kirsner JB, Shorter RG, eds. Inflammatory Bowel Disease, 4th Edn. Baltimore: Williams & Wilkins, 1995; 281-300.
175. Bjorsk S, Dahlstrom A, Johansson L, Ahlman H. Treatment of the mucosa with local anaestetics in ulcerative colitis. Agents Actions 1992; Special Conference Issue: C60-72.
176. Arlander E, Ost A, Stahlberg D, Lofberg R. Ropivocaine gel in active distal ulcerative colitis and proctitis - A pharmacokinetic and exploratory clinical study. Aliment Pharmacol Ther 1996; 10: 73-81.
177. Lechin F, Van der Dijs B, Insausti CL et al. Treatment of ulcerative colitis with clonidine. J Clin Pharmacol 1985; 25: 219-26.
178. Ardizzone S, Bollani S, Manzionna G, Bianchi Porro G. Efficacy of transdermal clonidine for mild to moderate active left-sided ulcerative colitis: A pilot study. Gastroenterology 1999; 116: G2892.
179. Cohen RD, Hanauer SB. Nicotine in ulcerative colitis. How does it work and how can we use it? Clin Immunother 1996; 5: 169-74.
180. Pullan RD, Rhodes J, Ganesh S et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med 1994; 330: 811-5.
181. Thomas GAO, Rhodes J, Mani V et al. Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med 1995; 332: 988-92.
182. Sandborn WJ, Tremaine WJ, Laighton JA et al. Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: A pilot study. Aliment Pharmacol Ther 1997; 11: 663-71.