Tumour necrosis factor inhibitors reduce the acute-phase response in hapten-induced colitis

Abstract

Background: Tumour necrosis factor (TNF) α has been implicated in the pathogenesis of inflammatory bowel disease. The aim of this study was to assess the contribution of TNF to the pathogenesis of hapten-induced colitis. Methods: Colitis was induced in Wistar rats using intracolonic instillation of the hapten trinitrobenzenesulphonic acid (TNBS) in ethanol. Animals were treated with monoclonal anti-TNF antibody (cTN3), an idiotype control antibody (CB0006) or pentoxifylline. Colonic and systemic inflammation was assessed quantitatively. Results: The use of either TNF inhibitor attenuated the acute-phase response in the early stages of colitis. Median (interquartile range (i.q.r.)) (α2-macroglobulin levels were reduced in animals pretreated with cTN3 (421 (279-915) μmol/ml) or pentoxifylline (567 (253-1454) μmol/ml) compared with levels in untreated colitic animals (1552 (1406-1998)μmol/ml) (P<0.001 and P=0.006, respectively). In established colitis, administration of anti-TNF antibodies resulted in an increase in median (i.q.r.) weight gain (percentage change in body-weigh): colitic animals -2.3 (- 5.5 to 9.2) per cent versus cTN3treated rats 15 (7.5-16.7) per cent; P< 0.05. Conclusion: The systemic response to TNBS-induced colitis appears to be at least partially dependent on TNF. This study did not provide evidence to support a role for TNF in the pathogenesis of colonic inflammation in this model.