Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy

Purpose: Whereas X-irradiation with high doses is established to exert pro- inflammatory effects, low-dose radiotherapy (LD-RT) with single fractions below 1.0 Gy and a total dose below 12 Gy is clinically well known to exert anti-inflammatory and analgesic effects on several inflammatory diseases and painful degenerative disorders. Experimental studies to confirm the effectiveness, the empirical dose and fractionation schemes, and the underlying radiobiological mechanisms are still fragmentary. Method: The anti- inflammatory efficiency of LD-RT was confirmed in several experimental in vitro and in vivo models. Results: In vitro studies revealed a variety of mechanisms related to the anti- inflammatory effect, in particular the modulation of cytokine and adhesion molecule expression on activated endothelial cells and leukocytes, and of nitric oxide (NO) production and oxidative burst in activated macrophages and native granulocytes. Conclusion: Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. It is, therefore, reasonable to assume that further molecular pathways and cellular components contribute to the antiinflammatory effect of LD-RT. This review discusses data and models revealing aspects of the mechanisms underlying the anti- inflammation induced by low doses of X-irradiation and may serve as a basis for systematic analyses, necessary to optimize LD-RT in clinical practice.