Abstract | BACKGROUND AND AIMS: To 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. METHODS: Endoscopic 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. RESULTS: CONCLUSIONS:
|
Authors | A Di Sabatino, R Ciccocioppo, B Cinque, D Millimaggi, R Morera, L Ricevuti, M G Cifone, G R Corazza |
Journal | Gut
(Gut)
Vol. 53
Issue 1
Pg. 70-7
(Jan 2004)
ISSN: 0017-5749 [Print] England |
PMID | 14684579
(Publication Type: Journal Article)
|
Chemical References |
- Antibodies, Monoclonal
- Gastrointestinal Agents
- Tumor Necrosis Factor-alpha
- Infliximab
- CASP3 protein, human
- Caspase 3
- Caspases
|
Topics |
- Adult
- Antibodies, Monoclonal
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Caspase 3
- Caspases
(metabolism, physiology)
- Cells, Cultured
- Crohn Disease
(drug therapy, immunology, pathology)
- Dose-Response Relationship, Immunologic
- Female
- Gastrointestinal Agents
(pharmacology, therapeutic use)
- Humans
- Immunity, Mucosal
(drug effects)
- Infliximab
- Intestinal Mucosa
(immunology, pathology)
- Male
- Middle Aged
- Signal Transduction
(drug effects)
- T-Lymphocyte Subsets
(drug effects, immunology)
- Treatment Outcome
- Tumor Necrosis Factor-alpha
(antagonists & inhibitors)
|