A new agent for tumour necrosis factor-alpha inhibition: In vitro effects of dipyridamole in Crohn's disease

2009 ◽  
Vol 69 (6) ◽  
pp. 696-702
Author(s):  
Sule Poturoglu ◽  
Sabahattin Kaymakoglu ◽  
Nuray Gurel Polat ◽  
Duygu Ibrisim ◽  
Emel Ahishali ◽  
...  
2005 ◽  
Vol 16 (5) ◽  
pp. 289-292 ◽  
Author(s):  
Geoffrey Williams ◽  
Asad A Khan ◽  
Franzjosef Schweiger

Infliximab, a monoclonal antibody directed against tumour necrosis factor-alpha, is an effective therapy for Crohn's disease. Though uncommon, serious opportunistic infections, including reactivation of tuberculosis, have occurred in patients after infliximab administration. Meningitis caused byListeria monocytogenesdeveloped in a 37-year-old man six days after the second infusion of infliximab. The patient, who also was treated with azathioprine and corticosteroids, had an uneventful recovery after a course of antibiotics. Several other recent reports have implicated infliximab therapy in the development of severeListeriainfections, particularly meningitis and sepsis. With the increasing use of tumour necrosis factor-alpha-neutralizing agents, clinicians should be aware of the risk of opportunistic infections caused byL monocytogenesin patients with Crohn's disease following infliximab treatment.


2019 ◽  
Vol 14 (3) ◽  
pp. 381-392
Author(s):  
Richard K Felwick ◽  
Geraint J R Dingley ◽  
Rocio Martinez-Nunez ◽  
Tilman Sanchez-Elsner ◽  
J R Fraser Cummings ◽  
...  

Abstract Background and Aims Mucosal healing is important in Crohn’s disease therapies. Epithelial homeostasis becomes dysregulated in Crohn’s, with increased permeability, inflammation, and diarrhoea. MicroRNAs are small non-coding RNAs that regulate gene expression and show changes in inflammatory bowel disease. Tumour necrosis factor alpha [TNFα] inhibitor protein 3 is raised in Crohn’s and regulates TNFα-mediated activation of NFκB. We investigated TNFα regulation by microRNA in Crohn’s disease [CD], and studied effects on epithelial permeability and inflammation. Methods Colonic epithelium from CD and healthy donor biopsies was isolated using laser capture microdissection, and microRNA was quantified. Tumour necrosis factor alpha inhibitor protein 3 was characterised immunohistochemically on serial sections. Expression effect of microRNA was confirmed with luciferase reporter assays. Functional barrier permeability studies and innate cytokine release were investigated with cell and explant culture studies. Results MicroRNA23a levels significantly increased in colonic Crohn’s epithelium compared with healthy epithelium. Luciferase reporter assays in transfected epithelial cells confirmed that microRNA23a repressed expression via the 3’ untranslated region of tumour necrosis factor alpha inhibitor protein 3 mRNA, coinciding with increased NFκB-mediated transcription. Immunohistochemical staining of TNFAIP3 protein in colonic biopsies was reduced or absent in adjacent Crohn’s sections, correlating inversely with microRNA23a levels and encompassing some intercohort variation. Overexpression of microRNA23a increased epithelial barrier permeability in a colonic epithelial model and increased inflammatory cytokine release in cultured explant biopsies, mimicking Crohn’s disease characteristics. Conclusions MicroRNA23a overexpression in colonic Crohn’s epithelium represses tumour necrosis factor alpha inhibitor protein 3, enhancing sensitivity to TNFα, with increased intestinal permeability and cytokine release.


2009 ◽  
Vol 23 (3) ◽  
pp. 185-202 ◽  
Author(s):  
Daniel C Sadowski ◽  
Charles N Bernstein ◽  
Alain Bitton ◽  
Ken Croitoru ◽  
Richard N Fedorak ◽  
...  

BACKGROUND: Guidelines regarding the use of infliximab in Crohn’s disease were previously published by the Canadian Association of Gastroenterology in 2004. However, recent clinical findings and drug developments warrant a review and update of these guidelines.OBJECTIVE: To review and update Canadian guidelines regarding the use of tumour necrosis factor-alpha antibody therapy in both luminal and fistulizing Crohn’s disease.METHODS: A consensus group of 25 voting participants developed a series of recommendation statements that addressed pertinent clinical questions and gaps in existing knowledge. An iterative voting and feedback process was used in advance of the consensus meeting in conjunction with a systematic literature review to refine the voting statements. These statements were brought to a formal consensus meeting held in Montreal, Quebec (March 2008), wherein each statement underwent discussion, reformulation, voting and subsequent revision until group consensus was obtained (at least 80% agreement).OUTCOME: The 47 voting statements addressed three themes: induction therapy, maintenance therapy and safety issues. As a result of the iterative process, 23 statements achieved consensus and were submitted for publication.CONCLUSION: In the past five years, tumour necrosis factor-alpha antagonist therapy has become a cornerstone in the management of moderate-to-severe Crohn’s disease refractory to conventional treatment algorithms. The evidentiary base supporting the use of these drugs in Crohn’s disease is substantial and strengthened by results from long-term clinical and molecular studies. However, significant gaps in knowledge exist, particularly with regard to treatment failure. Confidence in the safety of these drugs is increasing, provided that therapy is administered in a clinical setting in which potential complications can be readily recognized and treated.


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