The effect of inflammation severity and of treatment on the production and release of TNFα by colonic explants in inflammatory bowel disease

Background: Despite its pivotal role in mucosal inflammation, data on TNF alpha levels in inflammatory bowel diseases have been contradictory. Aim: To examine TNF alpha production in relation to the type and severity of inflammation and therapy, using colonic explant cultures. Materials and methods: Rectal mucosal biopsies from 271 paediatric patients (178 inflammatory bowel disease, 27 inflammatory controls, 66 normal) were cultured for 4 or 18 h. Basal TNF alpha tissue content and release into the medium were measured by ELISA and compared to histological severity and clinical parameters. Results: TNF alpha release as well as tissue-associated TNF alpha levels were significantly increased in rectal biopsies from involved inflammatory bowel disease tissue. The amount of TNF alpha correlated with inflammation severity scores. TNF alpha levels were higher at 18 compared to 4 h in all groups, whether inflamed or not. TNF alpha released from rectal biopsies was lower among treated patients at 18 h. The presence of proximal colonic involvement was associated with higher TNF alpha release by uninvolved Crohn's disease rectal biopsies compared to patients with ileitis alone. Conclusions: TNF alpha production and release is increased in involved rectal explants from inflammatory bowel disease. Anti-inflammatory treatment diminishes this response.