Mode of function of biological anti-TNF agents in the treatment of inflammatory bowel diseases

被引：32

作者：

Tilg, Herbert ^{[1
]}

Moschen, Alexander ^{[1
]}

Kaser, Arthur ^{[1
]}

机构：

[1] Med Univ Innsbruck, Dept Med, Div Gastroenterol & Hepatol, A-6020 Innsbruck, Austria

来源：

EXPERT OPINION ON BIOLOGICAL THERAPY | 2007年 / 7卷 / 07期

关键词：

adalimumab; certolizumab; Crohn's disease; infliximab; TNF-alpha; ulcerative colitis; TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; INFLIXIMAB INDUCES APOPTOSIS; PROPRIA T-LYMPHOCYTES; C-REACTIVE PROTEIN; CROHNS-DISEASE; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; ULCERATIVE-COLITIS; COMPLEMENT ACTIVATION;

D O I：

10.1517/14712598.7.7.1051

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

TNF-alpha has been identified as a major mediator in the pathophysiology of inflammation. Anti-TNF agents, either as a neutralising antibody or a soluble TNF receptor, have markedly influenced the clinical management of several chronic inflammatory disorders. Whereas it seems likely that neutralisation of soluble and membrane-bound TNF might be a key mechanism of any anti-TNF agent, the potential of the anti-TNF antibody infliximab to induce lymphocyte/monocyte apoptosis in Crohn's disease has been considered an additional important mechanism. Other potential mode of actions include induction of the anti-inflammatory cytokines IL-10 or TGF-beta via retrograde signalling or induction of a certain subset of regulatory T cells. Certolizumab, a pegylated fully human anti-TNF monoclonal antibody also effective in Crohn's disease, lacks the capacity to induce apoptosis. Therefore, the capacity to induce apoptosis and neutralisation of TNF alone are insufficient to explain clinical efficacy of anti-TNF agents in human inflammatory bowel diseases.

引用

页码：1051 / 1059

页数：9

共 70 条

[1] Infliximab downregulates interferon-γ production in activated gut T-lymphocytes from patients with Crohn's disease [J].

Agnholt, J ;

Kaltoft, K .

CYTOKINE, 2001, 15 (04) :212-222

[2] Mini-review: How T lymphocytes switch between life and death [J].

Arnold, Ruediger ;

Brenner, Dirk ;

Becker, Mareike ;

Frey, Christian R. ;

Krammer, Peter H. .

EUROPEAN JOURNAL OF IMMUNOLOGY, 2006, 36 (07) :1654-1658

[3]

Arnott IDR, 2000, AM J GASTROENTEROL, V95, P3326

[4] New concepts in the pathophysiology of inflammatory bowel disease [J].

Bamias, G ;

Nyce, MR ;

De La Rue, SA ;

Cominelli, F .

ANNALS OF INTERNAL MEDICINE, 2005, 143 (12) :895-904

[5] The immunological and genetic basis of inflammatory bowel disease [J].

Bouma, G ;

Strober, W .

NATURE REVIEWS IMMUNOLOGY, 2003, 3 (07) :521-533

[6] TUMOR-NECROSIS-FACTOR-ALPHA IN STOOL AS A MARKER OF INTESTINAL INFLAMMATION [J].

BRAEGGER, CP ;

NICHOLLS, S ;

MURCH, SH ;

STEPHENS, S ;

MACDONALD, TT .

LANCET, 1992, 339 (8785) :89-91

[7] Antiangiogenic effects of anti-tumor necrosis factor a therapy with infliximab in psoriatic arthritis [J].

Cañete, JD ;

Pablos, JL ;

Sanmartí, R ;

Mallofré, C ;

Marsal, S ;

Maymó, J ;

Gratacós, J ;

Mezquita, J ;

Mezquita, C ;

Cid, MC .

ARTHRITIS AND RHEUMATISM, 2004, 50 (05) :1636-1641

[8] Drug insight:: Antagonists of tumor-necrosis factor-α in the treatment of inflammatory bowel disease [J].

Chang, JT ;

Lichtenstein, GR .

NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY, 2006, 3 (04) :220-228

[9] Transmembrane tumor necrosis factor is a potent inducer of colitis even in the absence of its secreted form [J].

Corazza, N ;

Brunner, T ;

Buri, C ;

Rihs, S ;

Imboden, MA ;

Seibold, I ;

Mueller, C .

GASTROENTEROLOGY, 2004, 127 (03) :816-825

[10] Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease [J].

Corken Mackey, Ann ;

Green, Lanh ;

Liang, Li-ching ;

Dinndorf, Patricia ;

Avigan, Mark .

JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION, 2007, 44 (02) :265-267

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