EGCG INDUCES AN INFLAMMATORY PROFILE REDUCING M2 MACROPHAGES IN A MOUSE MODEL OF MDS.

Abstract

Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, has shown a range of beneficial effects, including the inhibition of M2 macrophage polarization. Macrophages are indispensable tissue components and play a significant role in the pathophysiology of hematopoietic malignancies. In myelodysplastic syndrome (MDS), macrophages exhibit more M2-related characteristics (alternatively activated), which generally have pro-tumor effects. Thus, the aim of this study was to assess the immunomodulatory potential of EGCG on macrophages in MDS. Female NHD13 transgenic mice and their wild-type littermates, at 10 weeks old, were administered EGCG at a dosage of 50 mg/kg per day, five times a week, intraperitoneally for four weeks. Prior to receiving treatment, NHD13+ mice displayed a decrease in leukocyte and platelet counts as well as hemoglobin levels, consistent with characteristics of the disease and documented findings. EGCG promoted the polarization of macrophages within the bone marrow (BM) milieu. This effect was in part through heightened expression of pro-inflammatory cytokines/M1 macrophage markers, specifically interleukin 6 (IL6) (p = 0.05) and tumor necrosis factor-alpha (TNF-α) (p = 0.05). Concurrently, there was a noteworthy attenuation in the levels of interleukin 4 (IL4) (p = 0.03), an established anti-inflammatory marker associated with the M2 macrophage phenotype. Additionally, the percentage of M2 macrophages (CD45+CD11b+F4/80+CD206+) underwent a substantial reduction (p = 0.002). In summary, EGCG effectively steers macrophage polarization towards the M1 phenotype within the bone marrow microenvironment. These findings highlight EGCG's potential therapeutic role as an immunomodulator in MDS, providing new perspectives for its use in the treatment of hematopoietic malignancies by influencing the immune response in the context of the disease.