Biologic therapies, namely
antibodies against
tumor necrosis factor-alpha (
TNF- alpha) or its receptors, have been recently introduced for the treatment of patients with
inflammatory bowel disease (IBD). In the present study the effects of
cloricromene, an agent with known antithrombotic actions and with demonstrated anti-
TNF- alpha activity were investigated in a rat model of experimental
colitis induced with dinitrobenzenesulphonic
acid (DNB)/
ethanol. We investigated three experimental groups: (i)
sham-
colitis with vehicle-treatment (controls, n = 6), (ii)
colitis with vehicle-treatment (saline, 0.1 ml s.c., daily) (DNB-V, n = 7), (iii)
colitis with
cloricromene-treatment (10 mg/kg/day s.c.; DNB-C, n = 8). After 7 days, the
weight gain, colon wet weight, macroscopic damage score, coagulation parameters, colon mucosal
myeloperoxidase activity (MPO), and tissue concentrations of
TNF- alpha and of macrophage inhibitory peptide-2 (MIP-2) were assessed. The macroscopic damage scores, colon wet weights, and tissue MIP-2 levels were significantly increased in untreated and in
cloricromene-treated rats compared with controls.
Cloricromene treatment was associated with a minor
body weight loss (p < 0.025) and significantly reduced tissue concentrations of MPO and
TNF-alpha (p < 0.02, both). Blood coagulation parameters were not affected by treatment. In the DNB-model treatment with
cloricromene effectively reduces tissue levels of
TNF- alpha and of
myeloperoxidase, whereas MIP-2 concentrations were not influenced. Blood coagulation parameters remained unchanged indicating safety of treatment. Since
biological therapies frequently fail to improve disease course of IBD, other
therapies with similar targets should be further investigated.