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

Abstract

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