TY - JOUR T1 - Erythropoietin Reduces the Development of Experimental Inflammatory Bowel Disease JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1272 LP - 1280 DO - 10.1124/jpet.104.073197 VL - 311 IS - 3 AU - Salvatore Cuzzocrea AU - Emanuela Mazzon AU - Rosanna Di Paola AU - Nimesh S. A. Patel AU - Tiziana Genovese AU - Carmelo MuiĆ  AU - Angelina De Sarro AU - Christoph Thiemermann Y1 - 2004/12/01 UR - http://jpet.aspetjournals.org/content/311/3/1272.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -