Rödel Franz, Kamprad Friedrich, Sauer Rolf, Hildebrandt Guido
Klinik und Poliklinik für Strahlentherapie, Universität Erlangen-Nürnberg.
Strahlenther Onkol. 2002 Jan;178(1):1-9. doi: 10.1007/s00066-002-0901-3.
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.
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.
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.
已知单次剂量在0.1至1.0 Gy之间的低剂量放疗（LD-RT）具有抗炎作用。尽管针对其临床疗效提出了不同机制，但仍仅有少量实验数据。本文聚焦于LD-RT的功能和分子层面。
LD-RT在临床研究中的抗炎疗效在骨关节炎和类风湿关节炎的实验模型中得到了证实。在佐剂性关节炎模型中，于急性炎症高峰期给予5×1.0 Gy以及5×0.5 Gy，可在临床和组织学上阻止疾病进展，且不影响现有的炎症迹象。在体外试验中分析了LD-RT对外周血单核细胞（PBMC）和内皮细胞（EC）黏附的影响。在照射后近4小时，0.3至0.7 Gy的剂量范围内，与未照射的对照相比，贴壁细胞的黏附达到相对最低水平。在PBMC中，可确定凋亡的间断增加，在0.3至0.5 Gy之间达到最大值，L-选择素的蛋白水解脱落、抗炎细胞因子白细胞介素10表达增加以及肿瘤坏死因子α下调，这些是观察到的黏附减少的潜在机制。相反，在内皮细胞中可观察到E-选择素表达减少以及转化生长因子β（TGFβ1）诱导增加，在0.5 Gy时达到最大值。已知迁移至炎症部位的巨噬细胞表达诱导型一氧化氮合酶（iNOS），其通过产生一氧化氮（NO）介导细胞毒性和免疫调节作用。在0.6至1.25 Gy剂量范围内对受刺激的巨噬细胞进行LD-RT可降低NO生成和iNOS蛋白表达，而不影响iNOS mRNA表达。
我们的实验数据证实了LD-RT在体外和体内的抗炎疗效，表明其对不同细胞成分和炎症机制有影响。PBMC与内皮细胞之间黏附的调节以及对活化巨噬细胞的作用可能介导了LD-RT的抗炎特性。正在进行的实验将有助于阐明分子机制。
