ArticleGut2004
Defective mucosal T cell death is sustainably reverted by infliximab in a caspase dependent pathway in Crohn's disease.
Article in Gut, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 189 citations in OpenAlex.
- Adalimumab for maintenance of remission in Crohn's disease.The Cochrane database of systematic reviews · 2020Pooled it
- Adalimumab for induction of remission in Crohn's disease.The Cochrane database of systematic reviews · 2019Pooled it
- Trial
- Variants of the CASP9 gene as candidate markers for primary response to anti-TNF therapy in Crohn's disease patients.Journal of applied genetics · 2023Article
- Spatiotemporal regulation of galectin-1-induced T-cell death in lamina propria from Crohn's disease and ulcerative colitis patients.Apoptosis : an international journal on programmed cell death · 2021Article
- Effect of Anti-TNF Therapy on Mucosal Apoptosis Genes Expression in Crohn's Disease.Frontiers in immunology · 2021Article
- Apoptosis in peripheral blood lymphocytes in intestinal tuberculosis and Crohn's disease: Implications to diagnostic differentiation.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2020Article
- Unexpected mechanism of colitis amelioration by artesunate, a natural product from Artemisia annua L.Inflammopharmacology · 2020Article
- Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease.Pharmaceutics · 2020Review
- Effects of Anti-Cytokine Antibodies on Gut Barrier Function.Mediators of inflammation · 2019Review
- An increased Bax/Bcl-2 ratio in circulating inflammatory cells predicts primary response to infliximab in inflammatory bowel disease patients.United European gastroenterology journal · 2018Article
- Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.The pharmacogenomics journal · 2018Article
- Apoptosis markers of circulating leukocytes are associated with the clinical course of inflammatory bowel disease.Gastroenterology and hepatology from bed to bench · 2018Article
- Death in the intestinal epithelium-basic biology and implications for inflammatory bowel disease.The FEBS journal · 2016Review
- Anti-TNFα therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation.Journal of medical virology · 2016Article
- Update on pathogenesis and predictors of response of therapeutic strategies used in inflammatory bowel disease.World journal of gastroenterology · 2015Review
- Ex vivo immunosuppressive effects of mesenchymal stem cells on Crohn's disease mucosal T cells are largely dependent on indoleamine 2,3-dioxygenase activity and cell-cell contact.Stem cell research & therapy · 2015Article
- Apoptosis and the FLIP and NF-kappa B proteins as pharmacodynamic criteria for biosimilar TNF-alpha antagonists.Biologics : targets & therapy · 2014Review
- CD25 and TNF receptor II reflect early primary response to infliximab therapy in patients with ulcerative colitis.United European gastroenterology journal · 2013Article
- Adalimumab treatment in Crohn's disease: an overview of long-term efficacy and safety in light of the EXTEND trial.Clinical and experimental gastroenterology · 2013Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsTo verify whether targeting defective mucosal T cell death underlies the sustained therapeutic benefit of infliximab in Crohn's disease, we explored its in vivo proapoptotic effect after 10 weeks of treatment, and its in vitro killing activity on lamina propria T cells (LPT) and peripheral blood T cells (PBT), both isolated from Crohn's disease patients.
methodsEndoscopic intestinal biopsies were collected from 10 Crohn's disease patients (six steroid refractory and four fistulising) before and after three consecutive infusions of infliximab, administered at week 0, 2, and 6 in a single intravenous dose (5 mg/kg), and from 10 subjects who proved to have functional diarrhoea. Apoptosis was determined in vivo by TUNEL assay, and in vitro by fluorescein isothiocyanate-annexin V/propidium iodide staining on LPT and PBT from Crohn's disease patients cultured with infliximab. The effect of the broad caspase inhibitor Z-VAD-FMK and the neutralising anti-Fas antibody ZB4 was tested in vitro on LPT and PBT treated with infliximab. Caspase-3 activity was determined by immunoblotting.
resultsIn Crohn's disease patients, infliximab treatment induced a sustained LPT apoptosis, still evident four weeks after the last infusion. In vitro infliximab induced death of LPT from Crohn's disease patients occurred via apoptosis rather than necrosis. LPT showed a higher susceptibility to infliximab induced apoptosis than PBT in Crohn's disease patients. The signalling pathway underlying the restoration of infliximab induced LPT apoptosis occurred via the caspase pathway but not Fas-Fas ligand interaction in Crohn's disease.
conclusionsThese findings demonstrate that apoptosis is the major mechanism by which infliximab exerts its killing activity on LPT in Crohn's disease. The sustained LPT proapoptotic action of infliximab, which extends far beyond its circulating half life, may be responsible for the sustained remission induced in Crohn's disease patients by infliximab retreatment.
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