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[摘要]：Recent clinical trials with anti-interleukin (IL)-12p40 antibodies in psoriasis and Crohn's disease patients have demonstrated the therapeutic efficacy of this approach and have validated IL-12/IL-23 as an attractive target for the development of effective new drugs for the treatment of autoimmune and inflammatory disorders. IL-23, a new member of the IL-12 family, shares the p40 subunit with IL-12, and is similarly inhibited by anti-IL-12p40 antibodies. Emerging data clearly indicate that IL-23 is essential for the expansion and survival of Th17 T-cells, which have been identified as responsible for many of the inflammatory autoimmune responses. Investigation of the regulation of the p40 and the IL-23-specific p19 subunits led to the finding of a selective and dominant role for c-Rel in activating their promoters. This review describes drugs reported to inhibit the production of IL-12/IL-23, recent studies on their mechanisms of action in modulating the expression of these cytokines, and their potency and selectivity. |
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