Title:Modulation of Inflammatory Immune Reactions by Low-Dose Ionizing Radiation: Molecular Mechanisms and Clinical Application
VOLUME: 19 ISSUE: 12
Author(s):F. Rodel, B. Frey, U. Gaipl, L. Keilholz, C. Fournier, K. Manda, H. Schollnberger, G. Hildebrandt and C. Rodel
Affiliation:Department of Radiation Therapy and Oncology, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Keywords:Biphasic dose response, discontinuous dose dependency, immune modulation, inflammation, ionizing radiation, low-dose
radiation therapy
Abstract:During the last decade, a multitude of experimental evidence has accumulated showing that low-dose radiation therapy (single
dose 0.5-1 Gy) functionally modulates a variety of inflammatory processes and cellular compounds including endothelial (EC),
mononuclear (PBMC) and polymorphonuclear (PMN) cells, respectively. These modulations comprise a hampered leukocyte adhesion to
EC, induction of apoptosis, a reduced activity of the inducible nitric oxide synthase, and a lowered oxidative burst in macrophages.
Moreover, irradiation with a single dose between 0.5-0.7 Gy has been shown to induce the expression of X-chromosome linked inhibitor
of apoptosis and transforming growth factor beta 1, to reduce the expression of E-selectin and L-selectin from EC and PBMC, and to
hamper secretion of Interleukin-1, or chemokine CCL20 from macrophages and PMN. Notably, a common feature of most of these
responses is that they display discontinuous or biphasic dose dependencies, shared with "non-targeted" effects of low-dose irradiation
exposure like the bystander response and hyper-radiosensitivity. Thus, the purpose of the present review is to discuss recent
developments in the understanding of low-dose irradiation immune modulating properties with special emphasis on discontinuous dose
response relationships.
