Influence of Urolithin A and Cholecalciferol on IFN-γ Production by Peripheral Blood Mononuclear Cells Under Normal Conditions and in the Presence of Products Released by Tumor Cells

Urolithin A is a polyphenolic metabolite of ellagic acid and ellagitannins that is produced by intestinal microbiota and has higher bioavailability than the parent polyphenols. Regarding acute inflammation modeling, urolithin A(5 μM) and a combination of urolithin Awith cholecalciferol (0.01 μM) were shown to reduce phytohemagglutinin-stimulated production of IFN-γ by peripheral blood mononuclear cells (PBMC) of healthy donors (by 19 and 27%, respectively). The ability of the growth medium obtained from cancer cell cultivation to reduce IFN-γ production by PBMC was used by us to evaluate the effect of urolithin A on the immunosuppressive effect of chronic inflammation. Addition to HeLa tumor cells (cervical adenocarcinoma) of urolithin A, which suppresses production of various immunoregulatory factors by tumor cells, reduced the ability of the medium in which the tumor cells were cultivated to suppress IFN-γ production by PBMC. Thus, it can be assumed that urolithin Adecreases the immunosuppressive potential of the tumor microenvironment.