초록 close

Colchicine has been shown to regulate the ex-pression of inflammatory gene, but this compound possesses much weaker anti-inflamatory activity. In this study, we synthesized a new colchicine derivative CT20126 and examined its immuno-modulatory property. CT20126 was found to have immunosuppressive effects by inhibiting lympho-cyte proliferation without cytotoxicity and effectively inhibit the transcriptional expression of the inflam-matory genes, iNOS, TNF-α, and IL-1β, in ma-crophages stimulated by LPS. This effect was nearly comparable to that of cyclosporine A. This com-pound also significantly suppressed the production of nitric oxide and Th1-related pro-inflammatory cytokines, IL-1β, TNF-α, and IL-2, with minimal suppression of Th2-related anti-inflammatory cyto-kines IL-4 and IL-10 in the sponge matrix allograft model. Moreover, administration of CT20126 pro-longed the survival of allograft skins from BALB/c mice (H-2d) to the dorsum of C57BL/6 (H-2b) mice. The in vivo immune suppressive e ffects of CT20126 were similar to that of cyclosporine A. These results indicate that this compound may have potential therapeutic value for transplantation rejection and other inflammatory diseases.