Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 21, 2007; 13(15): 2166-2173
Published online Apr 21, 2007. doi: 10.3748/wjg.v13.i15.2166
Therapeutic and prophylactic thalidomide in TNBS-induced colitis: Synergistic effects on TNF-α, IL-12 and VEGF production
Ana Teresa Carvalho, Heitor Souza, Antonio Jose Carneiro, Morgana Castelo-Branco, Kalil Madi, Alberto Schanaider, Flavia Silva, Fernando Antonio Pereira Jứnior, Márcia G Pereira, Cláudio Tortori, Ilana Dines, Jane Carvalho, Eduardo Rocha, Celeste Elia
Ana Teresa Carvalho, Heitor Souza, Antonio Jose Carneiro, Flavia Silva, Fernando Antonio Pereira Jứnior, Márcia G Pereira, Cláudio Tortori, Ilana Dines, Jane Carvalho, Eduardo Rocha, Celeste Elia, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Brazil
Morgana Castelo-Branco, Departamento de Histologia e Embriologia, Laboratório de Imunologia Celular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-590, Brazil
Kalil Madi, Laboratório Multidisciplinar de Pesquisa, Anatomia Patológica, Hospital Universitário Clementino Fraga Filho, Brazil
Alberto Schanaider, e Cirurgia Experimental, Hospital Universitário Clementino Fraga Filho, Brazil
Author contributions: All authors contributed equally to the work.
Correspondence to: Ana Teresa Carvalho, Departamento de Clínica Médica, Hospital Universitário Clementino Fraga Filho, Rua Barão da Torre, 666-101, Ipanema, Rio de Janeiro, RJ, Brazil, 22411-002, Brazil. atpugas@yahoo.com.br
Telephone: +55-21-25111612 Fax: +55-21-22551968
Received: December 19, 2006
Revised: January 10, 2007
Accepted: February 14, 2007
Published online: April 21, 2007
Abstract

AIM: To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor α (TNF-α), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohn’s disease (CD).

METHODS: Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-α and IL-12 were quantified in the supernatant of organ cultures by ELISA.

RESULTS: Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-α and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-α levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-α and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells.

CONCLUSION: Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-α, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

Keywords: Thalidomide; Experimental colitis; Inflammatory bowel disease; Tumor necrosis factor α; IL-12; Vascular endothelial growth factor