Tumour necrosis factor inhibitors reduce the acute-phase response in hapten-induced colitis.
BACKGROUND
Tumour necrosis factor (TNF) alpha 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.)) alpha 2-macroglobulin levels were reduced in animals pretreated with cTN3 (421 (279-915) micromol/ml) or pentoxifylline (567 (253-1454) micromol/ml) compared with levels in untreated colitic animals (1552 (1406-1998) micromol/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.


CONCLUSIONS
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. Presented in part to the 86th meeting of the Surgical Research Society in Nottingham, UK, 9-11 July 1997, and published in abstract form as Br J Surg 1997; 84: 1613
Armstrong
A M
AM
Department of Surgery, The Queen's University of Belfast, UK.
Foulkes
R
R
Jennings
G
G
Gannon
C
C
Kirk
S J
SJ
Gardiner
K R
KR
D000210:Acute-Phase Reaction / Q000517:prevention & control*; D000818:Animals; D000906:Antibodies / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D006241:Haptens; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D000906:Antibodies; D006241:Haptens; D014409:Tumor Necrosis Factor-alpha; D014302:Trinitrobenzenesulfonic Acid