Therapeutic effects of triptolide on interleukin-10 gene-deficient mice with colitis.

BACKGROUND: Triptolide, the principal active ingredient in the extract of Chinese herb Tripterygium wilfordii Hook , has both anti-inflammatory and immunomodulatory activities. However, the potential therapeutic role of triptolide in IBD was still unknown. Interleukin-10 deficient mice, a well characterized experimental model of inflammatory bowel disease, spontaneously developed a Th1 T cell-mediated colitis with many similarities to Crohn's disease. This study was designed to investigate the therapeutic effect of triptolide on the chronic colitis in IL-10-/- mice.

METHODS: Triptolide was intraperitoneally administrated every another day for 8 weeks to IL-10-/- mice. The gross and histological appearances of the colon, the level of inflammatory mediators and transcription factor activation in the colon were evaluated and compared with the control group.

RESULTS: The 8-week administration of triptolide resulted in a significant decrease in the severity of colitis, together with lower production of TNF-alpha ,IFN-gamma and IL-4 in colon. The level of serum amyloid A was decreased in triptolide-treated mice. Gene expressions of IL-12 and IL-23 in colon were also downregulated after treatment. Furthermore, administration of triptolide markedly reduced NF-small ka, CyrillicB activation in colon mucosa of IL-10-/- mice.

CONCLUSIONS: The efficacy of tritpolide treatment for the reduction of intestinal inflammation in IL-10-/- mice is a result of both anti-inflammatory and immunosuppressive activity. Triptolide holds significant potential for clinical applications for CD treatment.