Background With today’s treatment options good disease control is achieved in most patients suffering from Rheumatoid Arthritis (RA) and degenerative inflammatory musculoskeletal diseases. However, not all patients do respond, acquire therapy resistance or have to reduce medications due to adverse side reactions. Low dose-radiotherapy (LD-RT) has been used to reduce experienced pain levels, attenuate inflammation, and improve the quality of life.1–4 However, a lack of randomised trials and in vivo and ex vivo experiments in inflammatory model systems refrain from routine use. Preclinical in vitro models revealed anti-inflammatory effects of LD-RT in doses ranging from 0.1–1.0 Gy on immune cells such as macrophages and neutrophils. We therefore aimed to investigate the impact of LD-RT on inflammation and bone homeostasis in human TNF-α tg (hTNF-α tg) mice.
Material and methods Bone marrow-derived osteoclasts (OC) as well as murine and human fibroblast-like synoviocytes (FLS) were irradiated in an ex vivo setting and analysed using qPCR, ELISA, and flow cytometry. Inflamed joints of hTNF-α tg mice were locally irradiated (0.5 Gy, 250 kV, 15 mA) and monitored over a 30 day period. Paw sections were analysed using histomorphological methods and the OsteoMeasure™ Software.
Results We observed a significant improvement in grip strength in locally irradiated animals compared to controls. Consecutive analysis of paws showed a significant decrease in inflammatory areas alongside a reduction in OC-numbers and bone loss after irradiation with 0.5 Gy. Numbers of ex vivo differentiated OCs were also significantly reduced after exposure to doses ≥0.5 Gy. LD-RT of FLS led to a dose-dependent reduction of cell growth and increased cell death. Further, a reduction of pro-inflammatory cytokines could be observed in murine FLS after irradiation.
Conclusion Our findings support a positive effect of LD-RT on TNF-driven arthritis. Next to a considerably decelerating effect on inflammation, we revealed an impact on OCs and thus possibly on bone erosion. Future placebo controlled studies need to address the beneficial LD-RT effect in RA patients.
(Supported by the German Federal Ministry of Education and Research (GREWIS, 02NUK017G)).
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