Modulation of Inflammatory Reactions by Low-Dose Ionizing Radiation: Cytokine Release of Murine Endothelial Cells Is Dependent on Culture Conditions

BACKGROUND: In many European countries, patients with a variety of chronical inflammatory diseases are treated with low-dose radiotherapy (LD-RT). In contrast to high-dose irradiation given to tumor patients, little is known about radiobiological mechanisms underlying this clinical successful LD-RT application. The objective of this study was to gain a better insight into the modulation of inflammatory reactions after LD-RT on the basis of endothelial cells (EC) as major participants and regulators of inflammation. METHODS: Three murine EC lines were cultivated under 2D and 3D culture conditions and irradiated with doses from 0.01 Gy to 2 Gy. To simulate an inflammatory situation, cells were activated with TNF-α. After LD-RT, a screening of numerous inflammatory markers was determined by multiplex assay, followed by detailed analyses of four cytokines (KC, MCP-1, RANTES, and G-CSF). Additionally, the monocyte binding to EC was analyzed. RESULTS: Cytokine concentrations were dependent on culture condition, IR dose, time point after IR, and EC origin. IR caused nonlinear dose-dependent effects on secretion of the proinflammatory cytokines KC, MCP-1, and RANTES. The monocyte adhesion was significantly enhanced after IR as well as activation. CONCLUSIONS: The study shows that LD-RT, also using very low radiation doses, has a clear immunomodulatory effect on EC as major participants and regulators of inflammation.