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• Curcumin is a polyphenol derived from the dietary spice turmeric. It possesses diverse anti-inflammatory and anti-cancer properties. Curcumin has been shown to exhibit an inhibitory effect on the production of inflammatory cytokines by human monocytes and has inhibited the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE) in association with a decrease in interleukin 12 (IL-12) production and signal transducer and activator of transcription 4 (STAT4) activation. The type I interferon (IFN) IFN-B has the ability to suppress IL-12. Both IL-12 and IFN-alpha/beta signal through the activation by phosphorylation of STAT4. Our aim was to investigate the effects of curcumin on the ability of T cells to respond to IL-12 or IFN-alpha/beta. We report that curcumin decreases IL-12-induced STAT4 phosphorylation, IFN-gamma production, and IL-12 Rbeta1 and beta2 expression. IFN-beta-induced STAT4 phosphorylation, IL-10 production and IFN receptor (IFNAR) subunits 1 and 2 expression were enhanced by curcumin. Curcumin increased IFN-alpha-induced IL-10 and IFNAR1 expression. Prior exposure to curcumin decreased IFN-alpha-induced IFNAR2 expression and did not modify the level of IFN-alpha-induced pSTAT4 generation. Thus, the effect of curcumin on STAT4 activation in T cells is dependent upon the stimulus to which the T cells have been exposed.

...prior exposure to curcumin enhanced the ability of T cells to respond to IFN-B, not only at the level of cytokine induction but also upstream at the signalling pathway and receptor level.

We found that prior treat-ment with curcumin enhanced IFN-B-induced IL-10 production (an anti-inflammatory cytokine), whilst the induction of IFN-gamma (a pro-inflammatory cytokine) by IL-12 in human T cells was reduced by pre-treatment with curcumin.

Although it is clear that the differentiation of Th1 cells is crucial for an effective immunity to a wide variety of intracellular pathogens, Th1 cells and IL-12 may also contribute to the pathogenesis of a variety of immune-mediated inflammatory disorders, including MS and rheumatoid arthritis. It has already been shown that curcumin inhibits IL-12 production and signalling in EAE. This, combined with the inhibition of IL-12 signalling in human T cells and curcumin synergistic effect with IFN-B observed in this study on immune cells from both normal volunteers and MS patients, could place curcumin as a potential therapeutic agent in the treatment of MS.