Zytokin- und Antizytokintherapien bei chronisch entzündlichen Darmerkrankungen

Morbus Crohn und Colitis ulcerosa sind die häufigsten immunologisch vermittelten gastroenterologischen Erkrankungen. Funktionell wird eine chronisch persistierende Immunantwort beobachtet, die sich von der regulierten Aktivierung des intestinalen Immunsystems unter physiologischen Bedingungen oder bei akuten Infektionen unterscheidet [47] [56] . Als Pathomechanismus wird ein enges Zusammenspiel zwischen genetischer Suszeptibilität des Patienten, der mukosalen Immunregulation und der mikrobiologischen Darmflora vermutet.

Literatur

• 1 Akbar A, Lord J M, Salmon M. IFN-α and IFN-β: a link between immune memory and chronic inflammation.  Immunol Today. 2000;  21 337-342
• 2 Arnott I DR, Shand A, Ghosh S. Administration of Infliximab in Crohn’s disease does not deplete complement components C3 an C4.  Am J Gastroenterol. 2000;  95 3320-3321
• 3 Beutler B, Krochin N, Milsark I W, Luedke C, Cerami A. Control of cachectin (tumour necrosis factor) protects mice from lethal effect of endotoxin.  Science. 1986;  232 977-980
• 4 Bickston S J, Lichtenstein G R, Arseneau K O, Cohen R B, Cominelli F. The relationship between infliximab treatment and lymphoma in Crohn’s disease.  Gastroenterology. 1999;  117 1433-1437
• 5 Brandtzaeg P, Farstad I N, Haraldsen G. Regional specialization in the mucosal immune system; primed cells do not always home along the same track.  Immunol Today. 1999;  6 267-277
• 6 Braunstein J, Qiao L, Autschbach F, Schürmann G, Meuer S. T cells of the human intestinal lamina propria are high producers of interleukin-10.  Gut. 1997;  41 215-220
• 7 Choy E H, Rankin E C, Kassimos D. et al . The engineered human anti-tumor necrosis factor-alpha antibody CDP571 inhibits inflammatory pathways but not T cell activation in patients with rheumatoid arthritis.  J Rheumatol. 1999;  26 2310-2317
• 8 Cohen R D, Tsang J F, Hanauer S B. Infliximab in Crohn’s disease: first anniversary clinical experience.  Am J Gastroenterol. 2000;  95 3469-3477
• 9 D’Haens G, Swijsen C, Noman M, Lemmens L, Geboes K, Rutgeerts P. Etanercept (TNF receptor fusion protein, Enbrelš) is effective and well tolerated in active refractory Crohn’s disease: Results of a single center pilot trial.  Gastroenterology (Abs.). 2000;  118 3600
• 10 Desreumaux P, Brandt E, Bambiez L. et al . Distinct cytokine pattern in early and chronic ileal lesions of Crohn’s diease.  Gastroenterology. 1997;  113 118-126
• 11 Ehrenpreis E D, Kane S V, Cohen L B, Cohen R D, Hanauer S B. Thalidomide therapy for patients with refractory Crohn’s disease: an open-label trial.  Gastroenterology. 1999;  117 1271-1277
• 12 Eigler A, Loher F, Endres S. Suppression der Synthese des Tumornekrosefaktor.  Der Internist. 2001;  42 28-34
• 13 Evans R C, Clarke L, Heath P, Stephens S, Morris A I, Rhodes J M. Treatment of ulcerative colitis with an engineered anti-TNFα antibody CDP571.  Aliment Pharmacol Ther. 1997;  11 1031-1035
• 14 Farrell R J, Ang Y, Kileen P. et al . Increased incidence of non-Hodgkin’s lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low.  Gut. 2000;  47 514-519
• 15 Farrell R J, Shah S A, Lodhavia P J. et al . Clinical experience with infliximab therapy in 100 patients with Crohn’s disease.  Am J Gastroenterol. 2000;  95 3490-3497
• 16 Fedorak R N, Gangl A, Elson C O. et al . Recombinant human interleukin 10 in the treatment of patients with mild to moderate active Crohn’s disease.  Gastroenterology. 2000;  119 1473-1482
• 17 Fuss I J, Neurath N, Boirivant M. et al . Disparate CD4+ lamina propria 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 1261-1270
• 18 Gasche C, Reinisch W, Vogelsang H. et al . Prospective evaluation of interferon-alpha in treatment of chronic active Crohn’s disease.  Dig Dis Sci. 1995;  40 800-804
• 19 Geißler M, Blum H E. Therapeutische monoklonale Antikörper.  Dtsch Med Wschr. 2000;  125 1501-1504
• 20 Kempeni J. Update on D2E7: A fully human anti-tumour necrosis factor alpha monoclonal antibody.  Ann Rheum Dis. 2000;  59 i44-i45 (suppl))
• 21 Kugathasan S, Werlin S L, Martinez A, Rivera M T, Heikenen J B, Binion D G. Prolonged duration of response to infliximab in early but not late pediatric Crohn’s disease.  Am J Gastroenterol. 2000;  95 3189-3194
• 22 Lochs H, Adler G, Beglinger C. et al . Anti-TNF antibody in Crohn’s disease - status of information, comments and recommendations of an international working group.  Z Gastroenterol. 1999;  37 509-512
• 23 Maini R N, Elliott M, Brennan F M, Williams R O, Feldmann M. Targeting TNF alpha for the therapy of rheumatoid arthritis.  Clin Exp Rheumatol. 1994;  12 S63-S66 (Suppl 1))
• 24 Marth T, Zeitz M. Konventionelle und immunmodulatorische Therapie bei chronisch-entzündlichen Darmerkankungen.  Dtsch Med Wschr. 1999;  124 1173-1177
• 25 Menghini V V, Arora A S. Infliximab-associated reversible cholestatic liver disease.  Mayo Clin Proc. 2001;  76 84-86
• 26 Moreland L W, Baumgartner S W, Schiff M H. et al . Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p-75)-Fc fusion protein.  N Engl J Med. 1997;  340 1398-1405
• 27 Neurath M, Fuss I, Kelsall B L, Stüber E, Strober W. Antibodies to interleukin 12 abrogate established experimental colitis in mice.  J Exp Med. 1995;  182 1281-1290
• 28 Nicolaus S, Raedler A, Kuhbacker T, Sfikas N, Fölsch U R, Schreiber S. Mechanisms in failure of infliximab for Crohn’s disease.  Lancet. 2000;  356 1475-1479
• 29 Poltorak A, Peppel K, Beutler B. Receptor-mediated label-transfer assay (RELAY) - a novel method for the detection of plasma tumor necrosis factor at attomolar concentrations.  J Immunol Methods. 1994;  169 93-99
• 30 Present D H, Rutgeerts P, Targan S. et al . Infliximab for the treatment of fistulas in patients with Crohn’s disease.  N Engl J Med. 1999;  340 1398-1405
• 31 Qiao L, Braunstein J, Golling M. et al . Differential regulation of human T cell responsiveness by mucosal versus blood monocytes.  Eur J Immunol. 1996;  26 922-927
• 32 Qiu B S, Pfeiffer C J, Keith J CJ. Protection of recombinant human interleukin-11 against experimental TNB-induced colitis in rats.  Dig Dis Sci. 1996;  41 1625-1630
• 33 Ricart E, Pannaccione R, Loftus E V, Tremaine W J, Sandborn W J. Successful management of Crohn’s disease of the ileoanal pouch with infliximab.  Gastroenterology. 1999;  117 429-432
• 34 Rogler G, Brand K, Vogl D. et al . Nuclear factor kappa B is activated in macrophages and epithelial cells of inflamed intestinal mucosa.  Gastroenterology. 1998;  115 357-369
• 35 Rutgeerts P, D’Haens G, Targan S. et al . Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (Infliximab) to maintain remission in Crohn’s disease.  Gastroenterology. 1999;  117 761-769
• 36 Sandborn W J, Hanauer S B. Antitumor necrosis factor therapy for inflammatory bowel disease: A review of agents, pharmacology, clinical results, and safety.  Inflamm Bowel Dis. 1999;  5 119-133
• 37 Sands B E. Therapy of inflammatory bowel disease.  Gastroenterology. 2000;  118 S68-S82 (Suppl)
• 38 Sands B E, Bank S A, Sninsky C A. 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
• 39 Sands B E, Podolsky D K, Tremaine W J. et al . Chimeric monoclonal anti-tumor necrosis factor alpha antibody (cA2) in the treatment of severe, steroid-refractory ulcerative colitis.  Gastroenterology. 1996;  110 A1008
• 40 Schieferdecker H L, Ullrich R, Hirseland H, Zeitz M. T cell differentiation antigens on lymphocytes in human intestinal lamina propria.  J Immunol. 1992;  149 2816-2822
• 41 Schölmerich J. Which immunosuppressors do you use to treat Crohn’s diseae and ulcerative colitis? In which order of priority and how worried are you about toxicity?.  Inflamm Bowel Dis. 1998;  4 248-252
• 42 Schreiber S, Fedorak R N, Nielson O H. et al . Safety and efficacy of recombinant human interleukin-10 chronic active Crohn’s disease.  Gastroenterology. 2000;  119 1461-1472
• 43 Schreiber S, Fedorak R N, Wild G. et al . Safety and tolerance of rHuIL-10 treatment in patients with mild/moderate active ulcerative colitis.  Gastroenterology. 1998;  114 A1079
• 44 Sheldon D G, Sawchuk L L, Kozarek R A, Thirlby R C. Twenty cases of peristomal pyoderma gangrenosum.  Arch Surg. 2000;  135 564-569
• 45 Soykan I, Ertan C, Özden A. Severe anaphylactic reaction to infliximab: Report of a case.  Am J Gastroenterol. 2000;  95 2395-2396
• 46 Stack W A, Mann S D, Roy A J. et al . Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn’s disease.  Lancet. 1997;  349 521-524
• 47 Strober W, Fuss I J, Erhardt R O, Neurath M, Boirivant M, Ludviksson B R. Mucosal immune regulation and inflammatory bowel disease: new insights from murine models of inflammation.  Scand J Immunol. 1998;  48 453-458
• 48 Strober W, Neurath M F. Immunological diseases of the gastrointestinal tract. l. St. Louis: Mosby In: Rich, R. R., Ed. Book 1995: 1401-1428
• 49 Sümer N, Palabiyikoglu M. Induction of remission by interferon-alpha in patients with chronic active ulcerative colitis.  Eur J Gastroenterol Hepatol. 1995;  7 597-602
• 50 Targan S R, Hanauer S B, van Deventer S JH. 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 1029-1035
• 51 van Deventer S JH, Elson C O, Fedorak R N. Multiple doses of intravenous interleukin 10 in steroid-refractory Crohn’s disease. Crohn’s Disease Study Group.  Gastroenterology. 1997;  113 383-389
• 52 van Dullemen H M, van Deventer S JH, Hommes D W. et al . Treatment of Crohn’s disease with anti-tumor necrosis factor chimeric monoclonal antibody (cA2).  Gastroenterology. 1995;  109 129-135
• 53 Vantrappen G, Coremans G, Billiau A, De Somer P. Treatment of Crohn’s disease with interferon. A preliminary clinical trial.  Acta Clin Belg. 1980;  35 238-242
• 54 Vasiliauskas E A, Kam Y L, Abreu-Martin M T. et al . An open-label pilot study of low-dose thaliomide in chronically active, steroid-dependent Crohn’s disease.  Gastroenterology. 1999;  117 1278-1287
• 55 Vermeire S, Monsuur F, Groenen P, Peeters M, Vlietinck R, Rutgeerts P. Response to anti-TNFα-treatment is associated with the TNF-308.1 allele.  Gastroenterology. 2000;  118 3595
• 56 Zeitz M. Pathogenesis of inflammatory bowel disease.  Digestion. 1997;  58 59-61 (Suppl 1))
• 57 Zeitz M, Schieferdecker H L, Ullrich R, Jahn H U, James S P, Riecken E O. Phenotype and function of lamina propria T cells.  Immunol Res. 1991;  10 199-206

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