Resveratrol Modulates the Inflammatory Profile of Immune Responses and Circulating Endothelial Cells' (CECs') Population During Acute Whole Body Gamma Irradiation.

ABSTRACT

Wistar rats were whole body irradiated with a single dose of 2 Gy post administration with 10 or 100 mg/kg of resveratrol (RSV) intraperitoneally for 30 days. Rats' livers were dissected and processed to analyze immune response profiles of Th1, Th2, Th9, Th17, and Th22 by flow cytometry. In addition, peripheral blood samples were collected and circulating endothelial cells (CECs) were counted as an indicator for endothelial damage. Results demonstrated that resveratrol at 100 mg/kg enhanced liver immunological response influenced by irradiation by inducing Th2 immune response that was revealed by an increase in IL-10 secretion to more than 5,000 pmol/ml post irradiation. Results also indicated that RSV, at a dose of 100 mg/kg, decreased levels of the main pro-inflammatory cytokines such as INF-γ, IL-22, IL-17A, and GM-CSF post irradiation. In addition, the same RSV was bound to upregulate the expression of IL-10 mRNA in isolated Kupffer cells (KCs) and their secretion of IL-10 post irradiation. The result demonstrated that KCs were the central source of this anti-inflammatory response mediated mainly by IL10. These results, proposed for the first time, clearly states that RSV promotes IL-10 mediated immune resolution by Kupffer cells and not by hepatocytes. This implies that KCs have a crucial role in radiotherapy. Additionally, this study showed that RSV had an anti-apoptotic effect through re-increasing the number of CECs, which is implicated in irradiation damage. Result of the current work discloses novel findings about the potential of RSV as a radio-protector agent of a natural origin and suggests novel roles of KCs as a pharmacological target during radiation exposure.