Inhibition of interleukin-12 production in lipopolysaccharide-activated macrophages by curcumin.

Pharmacological control of interleukin-12 production may be a key therapeutic strategy for modulating immunological diseases dominated by type-1 cytokine responses. In this study we investigated the effects of curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1, 6-heptadiene-3,5-dione) on the production of interleukin-12 from mouse macrophages stimulated with lipopolysaccharide. Curcumin potently inhibited the production of interleukin-12 in a dose-dependent manner. The effect of curcumin on interleukin-12 p40 promoter activation was analyzed by transfecting RAW264.7 monocytic cells with p40 promoter/reporter constructs. The repressive effect mapped to a region in the p40 promoter containing a binding site for nuclear factor kappaB (p40-kappaB). Furthermore, activation of macrophages by lipopolysaccharide resulted in markedly enhanced binding activity to the kappaB site, which significantly decreased upon addition of curcumin. These results suggest that curcumin-induced inhibition of interleukin-12 production in macrophages may explain some of the biological effects of curcumin including its anti-inflammatory activity.