Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of the expression of
intercellular adhesion molecule-1 (ICAM-1) in the colon.
Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by
hypoxia. Here we investigate the effects EPO has on the development of experimental
colitis. To address this question, we used an experimental model of
colitis induced by
dinitrobenzene sulfonic acid (
DNBS). When compared with
DNBS-treated mice, EPO (1000 IU/kg day s.c.)-treated mice subjected to
DNBS-induced
colitis experienced significantly lower rates in the extent and severity of the histological signs of colon injury.
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. Neutrophil infiltration (determined by histology as well as an increase in
myeloperoxidase activity in the mucosa) was associated with up-regulation of
ICAM-1. Immunohistochemistry for
nitrotyrosine and
poly(ADP-ribose) showed an intense staining in the inflamed colon. On the contrary, the treatment of
DNBS-treated mice with EPO significantly reduced the degree of
diarrhea and
weight loss caused by administration of
DNBS. EPO also caused a substantial reduction of the degree of colon injury, the rise in
myeloperoxidase activity (mucosa), and the increase in staining (immunohistochemistry) for
nitrotyrosine as well as the up-regulation of
ICAM-1 caused by
DNBS in the colon. Thus, treatment of rat with EPO reduces the degree of
colitis caused by
DNBS. We propose that EPO may be useful in the treatment of
inflammatory bowel disease.