[Functional and molecular aspects of anti-inflammatory effects of low-dose radiotherapy].

PURPOSE

Low-dose radiotherapy (LD-RT) with single fractions between 0.1 and 1.0 Gy is known to exert an antiinflammatory effect. Although different mechanisms for the clinical efficiency were proposed, only few experimental data are still available. This paper focuses on functional and molecular aspects of LD-RT.

METHODS AND RESULTS

The antiinflammatory efficiency of LD-RT in clinical studies could be confirmed in experimental models of osteoarthritis and rheumatoid arthritis. In a model of adjuvants arthritis, 5 x 1.0 Gy as well as 5 x 0.5 Gy, given at the maximum of the acute inflammation, could prevent clinically and histologically progression of the disease without affecting existing signs of inflammation. The effect of LD-RT on the adhesion of peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) was analyzed in in-vitro assays. In the dose range between 0.3 and 0.7 Gy almost 4 hours after irradiation adherent cells reached a relative minimum of adhesion compared to unirradiated controls. In PBMC an discontinuous increase of apoptosis with a maximum between 0.3 and 0.5 Gy, the proteolytic shedding of L-selectin and an increased expression of the antiinflammatory cytokine interleukin 10 as well as downregulation of TNF alpha could be identified as potential mechanisms for the observed reduced adhesion. Conversely, reduced expression of E-selectin and an increased induction of transforming growth factor beta (TGF beta 1) with a maximum at 0.5 Gy could be observed in endothelial cells. Macrophages immigrating the site of inflammation are known to express inducible nitrix-oxide synthase (iNOS), which in turn mediates cytotoxic and immunmodulatory effects by producing nitric oxide (NO). LD-RT of stimulated macrophages within the dose range between 0.6 and 1.25 Gy reduced NO production and iNOS-protein expression without affecting iNOS-mRNA expression.

CONCLUSION

Our experimental data have confirmed the antiinflammatory efficiency of LD-RT in vitro and in vivo, indicating effects on different cellular components and mechanisms of inflammation. The regulation of the adhesion between PBMC and endothelial cells and the effects on activated macrophages may mediate the antiinflammatory properties of LD-RT. Ongoing experiments will help to clarify the molecular mechanism.