Conversely, polymerised polyphenols did not inhibit the binding of anti-mouse CD3e and anti-mouse CD8a to the CD3e and CD8a expressed on the cell surface. Taken together, our results strongly suggest that the polymerised polyphenols bind specifically to CD4 molecules and that CD4 plays a key role in induction of IFN-c and GM-CSF expression. In the present study, we clearly demonstrate that polymers, but not monomers, of phenylpropanoids induce cytokine production from murine splenocytes. Furthermore, polymerised polyphenols directly bind CD4, and inhibition of CD4 function significantly suppresses IFN-c and GM-CSF production in murine splenocytes; indicating that the immunomodulating effects of polymerised polyphenols are regulated, at least in part, by the CD4 molecule. Several reports have recently shown that hydroxycinnamic acid derivatives exert anti-inflammation activity through the suppression of NF-kB. However, polyphenol oxidase and Diatrizoic acid peroxidase often interfere with phenolic compounds contained in foods, resulting in polymerisation. Therefore, we consume high molecular weight polymerised polyphenols in our daily diet. Consequently, revealing the immunomodulating activities and their underlying mechanisms induced by polymerised polyphenols is crucial. Figures 1 and 2 show that polymerised phenylpropanoic acids, but not monomers, induce cell proliferation and cytokine production, especially IFN-c and GM-CSF, in murine splenocytes; implying that enzymatic polymerisation can confer immunoactivating properties to phenylpropanoic acids. Our results provide new insights into the functions of polyphenols. Both IFN-c and GM-CSF are known to play central roles in innate immunity. IFN-c is closely UNC0379 related to natural killer cell-associated anti-tumour activity. On the other hand, GM-CSF is essential for anti-microbial activities against viruses, bacteria, and fungi. As for functional foods, IFN-c and GM-CSF are important factors in the treatment of cancer and prevention of infectious diseases. Many functional foods, which are used in complementary and alternative medicines for cancer therapy, have the ability to induce the activation of the host immune system. In Japan, some mushrooms are widely used as a health food, thereby expecting pharmacological activity. The fruiting body of an edible Basidiomycetes mushroom, A. brasiliensis, rich in b-glucan induces NK cell activation through an IFN-c-dependent pathway. Moreover, research has revealed that GM-CSF is required for the immunoenhancing activities induced by fungal-derived b-glucans, and that this mushroom has polyphenol-related enzymes such as polyphenol oxidase, and peroxidase.