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| 1 | Molecular mechanism of action of anti-tumor necrosis factor antibodies in inflammatory bowel diseases显示文摘Anti-tumor necrosis factor(TNF) antibodies are successfully used in the therapy of inflammatory bowel diseases(IBD). However, the molecular mechanism of action of these agents is still a matter of debate. Apart from neutralization of TNF, influence on the intestinal barrier function, induction of apoptosis in mucosal immune cells, formation of regulatory macrophages as well as other immune modulating properties have been discussed as central features. Nevertheless, clinically effective anti-TNF antibodies were shown to differ in their mode-of-action in vivo and in vitro. Furthermore, the anti-TNF agent etanercept is effective in the treatment of rheumatoid arthritis but failed to induce clinical response in Crohn's disease patients, suggesting different contributions of TNF in the pathogenesis of these inflammatory diseases. In the following, we will review different aspects regarding the mechanism of action of anti-TNF agents in general and analyze comparatively different effects of each antiTNF agent such as TNF neutralization, modulation of the immune system, reverse signaling and induction of apoptosis. We discuss the relevance of the membranebound form of TNF compared to the soluble form for the immunopathogenesis of IBD. Furthermore, we review reports that could lead to personalized medicine approaches regarding treatment with antiTNF antibodies in chronic intestinal inflammation, by predicting response to therapy. | Ulrike Billmeier Walburga Dieterich Markus F Neurath Raja Atreya | 2016 | World Journal of Gastroenterology2016，22，42： | 19 |
| 2 | First case report of exacerbated ulcerative colitis after anti-interleukin-6R salvage therapy显示文摘We present the case of a 53-year-old woman with long-standing ulcerative colitis and severe, steroid-dependent disease course unresponsive to treatment with azathioprine, methotrexate, anti-TNF antibodies(infliximab, adalimumab) and tacrolimus, who refused colectomy as a therapeutic option. As the pro-inflammatory cytokine interleukin-6(IL-6) had been identified as a crucial regulator in the immunopathogenesis of inflammatory bowel diseases, we treated the patient with biweekly intravenous infusions of an anti-IL-6R antibody(tocilizumab) for 12 wk. However, no clinical improvement of disease activity was noted. In fact, endoscopic, histological and endomicroscopic assessment demonstrated exacerbation of mucosal inflammation and ulcer formation upon anti-IL-6R therapy. Mechanistic studies revealed that tocilizumab treatment failed to suppress intestinal IL-6 production, impaired epithelial barrier function and induced production of pro-inflammatory cytokines such as TNF, IL-21 and IFN-γ. Inhibition of IL-6 by tocilizumab had no clinical benefit in this patient with intractable ulcerative colitis and even led to exacerbation of mucosal inflammation. Our findings suggest that anti-IL-6R antibody therapy may leadto aggravation of anti-TNF resistant ulcerative colitis. When targeting IL-6, the differential responsiveness of target cells has to be taken into account, as IL-6 on the one side promotes acute and chronic mucosal inflammation via soluble IL-6R signaling but on the other side also strongly contributes to epithelial cell survival via membrane bound IL-6R signaling. | Raja Atreya Ulrike Billmeier Timo Rath Jonas Mudter Michael Vieth Helmut Neumann Markus F Neurath | 2015 | World Journal of Gastroenterology2015，21，45： | 5 |
| 3 | IL -35 mediates mucosal immune responses that protect agaainst T -cell -dependent colifts显示文摘 | Wirtz S Billmeier U Mchedlidze T | | 0，，05： | 1 |
| 4 | Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis 显示文摘 | Wirtz S Billmeier U Mchedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 5 | From physiology to dis- ease and targeted therapy: interleukin-6 in inflammation and in- flammation-associated carcinogenesis显示文摘 | Rath T Billmeier U Waldner MJ | 2015 | Arch Toxicol2015，89，4： | 1 |
| 6 | Interleukin-35 mediatesmucosal immune responses that protect against T-cell-dependentcolitis显示文摘 | Wirtz S Billmeier U McHedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 7 | Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis显示文摘 | Wirtz S Billmeier U McHedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 8 | Argininosuccinic aciduria: investigation of an affected family显示文摘 | Billmeier GJ Molinary SV Wilroy RS | 1974 | J Pediatr1974，84，1： | 1 |
| 9 | Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis显示文摘 | Wirtz S Billmeier U Mchedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 10 | Interleukin-35 mediates mucosal immune responses that protect against T-cell-dependent colitis显示文摘 | Wirtz S Billmeier U McHedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 11 | Exchange rate pass-through and monetary policy in Croatia显示文摘 | Andreas Billmeier Leo Bonato | 2004 | Journal of Comparative Economics2004，，3： | 1 |
| 12 | Intedeu- kin -35 mediates mucosal immune responses that protect against T - cell - dependent colitis 显示文摘 | Stefan Wirtz Ulrike Billmeier Tamuna Mchedlidze | 2011 | Gastroenterology2011，141，5： | 1 |
| 13 | Interleukin-35 mediates mucosal immune responses that protect against T-cell- dependent colitis 显示文摘 | Wirtz S Billmeier U Mchedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 14 | Interleukin-35 mediates mucosal immune responses that protect against T cell-dependent colitis显示文摘 | Wirtz S Billmeier U Mchedlidze T | 2011 | Gastroenterology2011，141，： | 1 |
| 15 | Interleukin-35 mediatesmucosal immune responses that protect against T-cell -dependentcolitis显示文摘 | Wirtz S Billmeier U McHedlidze T | 2011 | Gastroenterology2011，141，5： | 1 |
| 16 | Phase II study of topotecan and thalidomide in patients with high -risk myelodysplastic syndromes显示文摘 | Raza A Lisak L Billmeier J | 2006 | Leuk lymphoma2006，47，3： | 1 |
| 17 | Lead poisoning from ingestion of Chinese herbal medicine显示文摘 | CHAN H BILLMEIER G J Jr EVANS W E | 1977 | Clin Toxicol1977，10，3： | 1 |
| 18 | Phase Ⅱ study of topotecan and thalidomide in patients with high-risk myelodysplastic syndromes 显示文摘 | Raza A Lisak L Billmeier J | 2006 | Leuk Lymphoma2006，47，3： | 1 |
| 19 | 为岁月镀上金色的光华显示文摘清晨的阳光爬满窗棂,清新而温暖,窗台上的花儿散发着淡淡的香气,沁人心脾。一个人的时光,你可以坐拥一杯茶的安暖,看蔚蓝的天空上白云悠悠,让一颗心在尘世浮躁中安静下来,感悟生活带给我们的点点滴滴的美好,在时光的百转干回中,品味岁月的静好。光阴茬苒,流年轻叹,每个人的心里都装着岁月的痕迹。当我们踩着岁月的台阶一步步地走向成熟,当我们睡眼惺忪地发现自己已不再年轻时。 | Alan Wisniewski Alvaro Goula & Pablo Figuera Cristian Mohaded David Green & Eugenie De Loynes Daevas Design Gingerlily JSPR Kateryna Sokolova Lena Billmeier & David Baur Mme Mina Ben Miled Maud Opdebeck Peter Karpf Simla Sa Simon Legald 伏平 范嘉苑 | 2016 | 现代装饰(家居)2016，0，5： | 0 |
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