[Study the effect and mechanism of thalidomide in model of inflammatory bowed disease].
OBJECTIVE
To assess the effect of thalidomide on Trinitrobenzensulphonic acid (TNBS)-induced or oxazolone-induced colitis and discuss the possible mechanism of its action.


METHODS
Transmural colitis was induced by TNBS in three groups of rats (n=6 each), and distal colitis was induced by oxazolone in three groups of rats (n=6 each). Then the rats of the groups were treated with thalidomide [200 mg/(kg x d)], prednisone [5 mg/(kg x d)] or vehicle (olive oil) respectively by oral gavage. The colitis was allowed to run its course for 7 d after gavage and at that time the following endpoints were assessed. Colitis was evaluated by macroscopic and microscopic score; the expression of NF-kappaB P65 was examined by immunohistchemical (IHC); the expression of TNF-alpha mRNA was assayed by hybridization in situ (ISH); the cytokine TNF-alpha, IL-4, IFN-gamma were estimated by enzyme-linked immunoadsordent assay (ELISA).


RESULTS
With respect to TNBS model, in the control, prednisone-treatment and thalidomide-treatment groups, the macroscopic and microscopic scores were 6.33 +/- 1.03, 1.67 +/- 0.82, 2.00 +/- 0.89 and 7.33 +/- 1.03, 2.67s +/- 0.82, 3.17 +/- 0.75 respectively; the expression levels of NF-kappaB P65 and TNF-alpha mRNA in the three groups were 62.45 +/- 12.38, 23.62 +/- 8.54, 34.18 +/- 9.65 and 12.42 +/- 4.63, 9.86 +/- 3.29, 4.35 +/- 1.74 respectively; the levels of TNF-alpha, IL-4, IFN-gamma were 540.32 +/- 80.76, 94.58 +/- 14.45, 486.18 +/- 68.47; 396.53 +/- 92.42, 78.45 +/- 12.69, 347.56 +/- 82.94; and 385.68 +/- 88.57, 123.68 +/- 38.15, 378.27 +/- 90.65 respectively. The results indicated that thalidomide treatment significantly reduced colonic inflammation, suppressed NF-kappaB activation,enhanced TNF-alpha mRNA degradation, inhibited the synthesis of the TNF-alpha, IEN-gamma and increased the production of IL-4. However, with respect to oxazolone model, the macroscopic score and microscopic score were 2.00 +/- 0.89, 0.33 +/- 0.52, 1.83 +/- 0.75 and 7.83 +/- 1.47, 3.33 +/- 0.82, 6.50 +/- 1.22 respectively. Thalidomide appeared not to be effective in reducing the oxazolone-induced chronic colitis.


CONCLUSIONS
Thalidomide may be proposed as a useful drug for Crohn's disease, but further work is needed to clarify whether it is an efficacious agent for ulcerative colitis.
Wang
Xuan
X
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Ouyang
Qin
Q
D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy; D003424:Crohn Disease / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy*; D016328:NF-kappa B / Q000378:metabolism; D010081:Oxazolone; D051381:Rats; D017207:Rats, Sprague-Dawley; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid
D016328:NF-kappa B; D010081:Oxazolone; D013792:Thalidomide; D014302:Trinitrobenzenesulfonic Acid