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

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Abstract
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. 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. 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-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. 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. © 2001 British Journal of Surgery Society Ltd