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Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules 被引量:18

Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules
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摘要 The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-α monoclonal antibody, infiiximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab. Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Antiinterferon-γ and anti-CD25 therapies were developed, but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach. Antibodies against α4 integrin and α4β7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 (ICAM-1) may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD. 煽动性的肠疾病(IBD ) 的病原学还没被澄清了,非明确地减少发炎和免疫的抑制免疫力的代理人为 IBD 在常规治疗被使用了。证据显示在 IBD 的内脏的粘膜免疫的 dysregulation 引起煽动性的 cytokines 和受动器白血球的交通国王的生产过剩进肠,因此导致不受管束的肠的发炎。在 IBD 的致病的理解的如此的最近的进展创造了明确地禁止涉及煽动性的串联的分子的新奇生物制品疗法的一个最近的趋势。为如此的处理的主要目标是煽动性的 cytokines 和他们的受体,和粘附分子。妄想的 anti-TNF-alpha 单音的同种细胞的抗体, infliximab,为 CD 成为了标准治疗,它也是可能的为 UC 有益。几 anti-TNF 试剂被开发了,但是他们中的大多数似乎不象 infliximab 一样有效。人性化的 anti-TNF 单音的同种细胞的抗体, adalimumab 可能为输了的病人的治疗是有用的应答的海角或发达不耐到 infliximab。对 IL-12 p40 和 IL-6 受体的抗体能是为 IBD 的其他的新 anti-cytokine 治疗。Anti-interferon-gamma 和 anti-CD25 治疗被开发,但是这些代理人的利益还没被建立了。进肠的白细胞移行的选择堵住似乎是一条好途径。对 alpha4 integrin 和 alpha4beta7 integrin 的抗体为 IBD 显示出利益。细胞间的粘附分子 1 的 Antisense oligonucleotide (ICAM-1 ) 可能为 IBD 是有效的。如此的混合物的临床的试用最近也被报导了或当前是在进行之中的。在这篇文章,我们为 IBD 考察如此的新奇生物制品疗法的功效和安全。
出处 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第29期4628-4635,共8页 世界胃肠病学杂志(英文版)
关键词 Inflammatory bowel disease CYTOKINE Adhesion molecule TREATMENT 炎症肠炎 治疗 细胞活素类 肠炎综合症
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  • 1[1]Strober W,Nakamura K,Kitani A.The SAMP1/Yit mouse:another step closer to modeling human inflammatory bowel disease.J Clin Invest 2001; 107:667-670
  • 2[2]Bouma G,Strober W.The immunological and genetic basis of inflammatory bowel disease.Nat Rev Immunol 2003; 3:521-533
  • 3[3]Fiocchi C.Inflammatory bowel disease:etiology and pathogenesis.Gastroenterology 1998; 115:182-205
  • 4[4]Murch SH,Braegger CP,Walker-Smith JA,MacDonald TT.Location of tumour necrosis factor alpha by immunohistochemistry in chronic inflammatory bowel disease.Gut 1993;34:1705-1709
  • 5[5]Breese EJ,Michie CA,Nicholls SW,Murch SH,Williams CB,Domizio P,Walker-Smith JA,MacDonald TT.Tumor necrosis factor alpha-producing cells in the intestinal mucosa of children with inflammatory bowel disease.Gastroenterology 1994;106:1455-1466
  • 6[6]Braegger CP,Nicholls S,Murch SH,Stephens S,MacDonald TT.Tumour necrosis factor alpha in stool as a marker of intestinal inflammation.Lancet 1992; 339:89-91
  • 7[7]Powrie F,Leach MW,Mauze S,Menon S,Caddie LB,Coffman RL.Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells.Immunity 1994; 1:553-562
  • 8[8]Kosiewicz MM,Nast CC,Krishnan A,Rivera-Nieves J,Moskaluk CA,Matsumoto S,Kozaiwa K,Cominelli F.Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease.J Clin Invest 2001; 107:695-702
  • 9[9]Van den Brande JM,Braat H,van den Brink GR,Versteeg HH,Bauer CA,Hoedemaeker I,van Montfrans C,Hommes DW,Peppelenbosch MP,van Deventer SJ.Infliximab but not etanercept induces apoptosis in lamina propria T-lymphocytes from patients with Crohn's disease.Gastroenterology 2003; 124:1774-1785
  • 10[10]Targan SR,Hanauer SB,van Deventer SJ,Mayer L,Present DH,Braakman T,DeWoody KL,Schaible TF,Rutgeerts PJ.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 JMed 1997; 337:1029-1035

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