BACKGROUND: Thalidomide could relieve clinical symptoms and intestinal mucosal 
lesions effectively in children with refractory inflammatory bowel disease (IBD) 
from the pre-clinical study. This study aimed to observe the therapeutic effect 
of thalidomide by the established animal model of IBD model of 
2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in Sprague-Dawley 
(SD) rats and to investigate the possible mechanism of action.
METHODS: A total of 82 SD rats of about 4-5 weeks were randomly divided into 
three groups: the control group (25 rats), TNBS-treated group (29 rats), and 
thalidomide treatment group (28 rats). Daily activities were recorded. At least 
eight rats from each group were killed on the 4th, 7th, and 14th days. 
Morphological and histological changes in the colon were individually assessed. 
Serum was collected and the levels of TNF-α and interleukins (IL-1β and IL-10) 
were assayed by ELISA method. The expression of colonic mucosal nuclear factor 
(NF)-κB was assayed with the immunohistochemical method.
RESULTS: (1) In the control group, diarrhea and rectal bleeding recovered 
rapidly and no death was recorded. In the TNBS-treated group, diarrhea and 
rectal bleeding persisted for a longer time. The mortality rate was 10.34% 
during the observation period. In the thalidomide treatment group, diarrhea and 
rectal bleeding persisted for a significantly shorter time than the TNBS-treated 
group (P < 0.01). The rats of this group also exhibited faster weight gain on 
day 7 compared with the TNBS-treated group but still lower than that of the 
control group. The mortality rate of the thalidomide treatment group was 3.57%. 
(2) Macroscopic and microscopic scores of the thalidomide-treated group were 
significantly lower than those of the TNBS model group on the 14th day (P < 
0.01). These results suggested faster and better colonic recovery in the 
thalidomide-treated group. (3) NF-κB expression in the colonic mucosa of the 
control group was lower than in the others, mainly distributed in the cytoplasm. 
A large amount of intra-nuclear and cytoplasm staining was observed (more 
prominently intra-nuclear) in the TNBS model group and the thalidomide treatment 
group. On the 7th and 14th days, intra-nuclear NF-κB-containing cells in the 
thalidomide treatment group were still significantly lower than those in the 
TNBS model group (P < 0.01). (4) In the control group, the cellular inflammatory 
factors (TNF-α, IL-1β, and IL-10) were expressed at a low level while in the 
other two groups they were already expressed at a significantly higher level on 
day 4. On day 7 the expressions of TNF-α and IL-1β in the thalidomide treatment 
group were lower than in the TNBS model group. On day 14, the expressions of 
TNF-α and IL-1β in the thalidomide treatment group were significantly lower than 
in the TNBS model group (P < 0.05). On day 4, the IL-10 levels of the 
thalidomide treatment group became significantly elevated. The levels gradually 
decreased but still remained at a higher level. In the TNBS model group, the 
IL-10 expression peaked later than in the thalidomide treatment group.
CONCLUSIONS: Thalidomide was effective in the management of TNBS-induced colitis 
in young rats. This may be due to the suppression and down-regulation of NF-κB 
and the expression of the downstream inflammatory mediators (TNF-α and IL-1β). 
There is also indication that the expression of the anti-inflammatory cytokine 
(IL-10) is concomitantly up-regulated as well.