Polyphenolic extract (PE) from olive oil exerts a potent immunomodulatory effect and prevents graft-versus-host disease in a mouse model

Abstract Polyphenols are a group of chemical substances found in plants, with immunomodulatory, anti-proliferative and anti-inflammatory properties that might be useful in the prophylaxis and treatment of graft-versus-host disease (GVHD). Polyphenolic extract (PE) obtained from extra virgin olive oil (EVOO) decreased the activation and proliferation of activated T-cells. In addition, a decreased production of pro-inflammatory cytokines was observed upon exposure to PE. Western-blot assays showed a marked inhibition of Akt phosphorylation and nuclear translocation of NFkB in activated T-cells. In a murine model of acute graft-versus-host disease (GVHD), we observed that mice which received a diet supplemented in PE (600 ppm) presented a higher survival rate and lower risk of developing GVHD when compared with the group that received control diet. Histopathological examination showed a significantly lower gut involvement in mice receiving PE, with a decrease in pro-inflammatory cytokines (Il-2, Il-17 and TNF-α) in serum and the reestablishment of butyrate concentration in the gut. In conclusion, PE obtained from EVOO exerts a potent immunomodulatory effect reducing the activation and proliferation of activated T-cells and the production of pro-inflammatory cytokines. In a murine model of acute GVHD, PE supplemented diet reduced the incidence and severity of the disease and increased survival after transplantation.