The immunological and genetic pathogeneses of
inflammatory bowel disease (IBD) have been well studied but not well elucidated in the recent years. Accordingly, the pharmacological treatment of IBDs is focusing upon the individual pathologic step (targeting
therapy). It has been shown recently that new drugs such as
biological immunomodulating agents and anti-inflammatory
cytokines have better short-term effects in some respects than the conventional drugs, and they might change the treatment strategy of IBDs in the near future. The aim of the present study was to examine the effects of
thalidomide treatment in the development of experimental
colitis. To address this question, we used an experimental model of
colitis, induced by
dinitrobenzene sulfonic acid (
DNBS).
DNBS-treated mice experienced
diarrhea and
weight loss. At 4 days after administration of
DNBS, the mucosa of the colon exhibited large areas of
necrosis. The observed mucosa alteration was associated with the colon production of
tumor necrosis factor (
TNF)-alpha,
interleukin (IL)-1beta, and
vascular endothelial growth factor (
VEGF). Neutrophil infiltration (determined by histology as well as an increase in
myeloperoxidase activity in the mucosa) was associated with an upregulation of
intercellular adhesion molecule-1. Immunohistochemistry for
nitrotyrosine and
poly (ADP ribose) showed an intense staining in the inflamed colon. When compared with
DNBS-treated mice,
thalidomide-treated (200 mg/kg orally) mice subjected to
DNBS-induced
colitis experienced a significantly lower rate in the extent and severity of the histological signs of colon injury.
Thalidomide also caused a substantial reduction of the rise in
myeloperoxidase activity (mucosa), in the increase in the tissue levels of
TNF-alpha, IL-1beta, and
VEGF, in the increase in staining (immunohistochemistry) for
nitrotyrosine and for
poly (ADP ribose), as well as in the upregulation of
intercellular adhesion molecule-1 caused by
DNBS in the colon. Thus,
thalidomide treatment reduces the degree of
colitis caused by
DNBS. We propose that this evidence may help to clarify the therapeutic actions of
thalidomide in patients with
Crohn's disease.