title: Therapeutic and prophylactic thalidomide in TNBS-induced colitis: synergistic effects on TNF-alpha, IL-12 and VEGF production.
abstract: OBJECTIVE
  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 alpha (TNF-alpha), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohnos 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-alpha 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-alpha and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-alpha levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-alpha and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells.
  
  
  CONCLUSIONS
  Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-alpha, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.
authors.affiliation: Departamento de Clinica Medica, Hospital Universitario Clementino Fraga Filho, Rua Barao da Torre, 666-101, Ipanema, Rio de Janeiro, RJ, Brazil. atpugas@yahoo.com.br
authors.forename: Ana Teresa
authors.initials: AT
authors.lastname: Carvalho
authors.forename: Heitor
authors.initials: H
authors.lastname: Souza
authors.forename: Antonio Jose
authors.initials: AJ
authors.lastname: Carneiro
authors.forename: Morgana
authors.initials: M
authors.lastname: Castelo-Branco
authors.forename: Kalil
authors.initials: K
authors.lastname: Madi
authors.forename: Alberto
authors.initials: A
authors.lastname: Schanaider
authors.forename: Flavia
authors.initials: F
authors.lastname: Silv
authors.forename: Fernando Antonio
authors.initials: FA
authors.lastname: Pereira Junior
authors.forename: Marcia G
authors.initials: MG
authors.lastname: Pereira
authors.forename: Claudio
authors.initials: C
authors.lastname: Tortori
authors.forename: Ilana
authors.initials: I
authors.lastname: Dines
authors.forename: Jane
authors.initials: J
authors.lastname: Carvalho
authors.forename: Eduardo
authors.initials: E
authors.lastname: Rocha
authors.forename: Celeste
authors.initials: C
authors.lastname: Elia
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D018664:Interleukin-12; D013792:Thalidomide; D014302:Trinitrobenzenesulfonic Acid