Thalidomide treatment reduces colon injury induced by experimental colitis.
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.
Mazzon
Emanuela
E
Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina Torre Biologica, Policlinico Universitario, 98123 Messina, Italy.
Muià
Carmelo
C
Di Paola
Rosanna
R
Genovese
Tiziana
T
De Sarro
Angelina
A
Cuzzocrea
Salvatore
S
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D013792:Thalidomide / Q000378:metabolism / Q000494:pharmacology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D013792:Thalidomide; D009195:Peroxidase