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

Background: Tumour necrosis factor (TNF) alpha has been implicated in the p athogenesis of inflammatory bowel disease. The aim of this study was to ass ess 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 wer e treated with monoclonal anti-TNF antibody (cTN3), an idiotype control ant ibody (CB0006) or pentoxifylline. Colonic and systemic inflammation was ass essed quantitatively. Results: The use of either TNF inhibitor attenuated the acute-phase respons e in the early stages of colitis. Median (interquartile range (i.q.r.)) alp ha (2)-macroglobulin levels were reduced in animals pretreated with cTN3 (4 21 (279-915) mu mol/ml) or pentoxifylline (567 (253-1454) mu mol/ml) compar ed with levels in untreated colitic animals (1552 (1406-1998) mu mol/ml) (P < 0.001 and P = 0.006, respectively). In established colitis, administrati on of anti-TNF antibodies resulted in an increase in median (i.q.r.) weight gain (percentage change in body-weight): colitic animals -2.3 (- 5.5 to 9. 2) per cent versus cTN3-treated 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 su pport a role for TNF in the pathogenesis of colonic inflammation in this mo del.