Radon Improves Clinical Response in an Animal Model of Rheumatoid Arthritis Accompanied by Increased Numbers of Peripheral Blood B Cells and Interleukin-5 Concentration

Abstract

Radon treatment is used as an established therapy option in chronic painful inflammatory diseases. While analgesic effects are well described, little is known about the underlying molecular effects. Among the suspected mechanisms are modulations of the anti-oxidative and the immune system. Therefore, we aimed for the first time to examine the beneficial effects of radon exposure on clinical outcome as well as the underlying mechanisms by utilizing a holistic approach in a controlled environment of a radon chamber with an animal model: K/BxN serum-induced arthritic mice as well as isolated cells were exposed to sham or radon irradiation. The effects on the anti-oxidative and the immune system were analyzed by flow-cytometry, qPCR or ELISA. We found a significantly improved clinical disease progression score in the mice, alongside significant increase of peripheral blood B cells and IL-5. No significant alterations were visible in the anti-oxidative system or regarding cell death. We conclude that neither cell death nor anti-oxidative systems are responsible for the beneficial effects of radon exposure in our preclinical model. Rather, radon slightly affects the immune system. However, more research is still needed in order to fully understand radon-mediated effects and to carry out reasonable risk-benefit considerations.

Experimental Setups for In Vitro Studies on Radon Exposure in Mammalian Cells—A Critical Overview

“…Opposing results were found by Deloch et al, who also analyzed the apoptotic and necrotic rate using Annexin-V/PI staining in monocytes, macrophages and bone marrow isolated from mice [70]. After radon exposure, no significant changes in apoptosis were observed when compared to sham-irradiated control samples.…”

“…However, if one aims to go beyond initial validation experiments, it is important to select a cell line of relevance to the pre-and neoplastic transformation which might be induced by radon exposure. Furthermore, there are a handful of studies which used malignant, immortalized cell lines for their in vitro experiments with radon analogues [46,101,113,114,117] and a large proportion of studies worked with blood or bone marrow cells [60,70,72,74,75,79,80,93,97,98,103,110,112]. The latter is relevant to investigate the effect of radon exposure on the immune system, which could have repercussions on the development of hypersensitivity and increase susceptibility to infections and lung cancer [143].…”

“…Furthermore, these studies are also very interesting in the context of radon treatments for chronic painful inflammatory diseases, which remains a controversial application [22,70]. In addition to the radiation protection and clinical applications, blood cells and particularly HPBLs are commonly used in radiobiology studies since they can be easily sampled for biodosimetry studies and circulating lymphocytes are a synchronic non-cycling population in G0/G1, which makes it easier to rule out and control cell cycle effects [144].…”

“…In principle, it is also possible to transfer this technique to non-adherent cells, such as human peripheral blood lymphocytes (HPBLs), by pre-coating Transwell ® inserts overnight with poly-l-lysine and poly-ornithine and therefore allow adhesion of the non-adherent cells [66,69]. Other groups removed the medium above the cells completely [67] or minimized the amount of culture medium (750 µL) in the culture plates where cells were seeded [70], resulting in a minimal diffusion barrier.…”

Effects of serial radon spa therapy on pain and peripheral immune status in patients suffering from musculoskeletal disorders– results from a prospective, randomized, placebo-controlled trial

“…Evidence for an anti-inflammatory shift of the immune system following therapeutic radon exposure comes from an arthritic mouse model, as well as from several patient studies, including the prospective, observatory RAD-ON01 trial ( 21 – 24 ). In the latter, serum cytokine concentrations, peripheral immune cell counts and their activation state were modulated in patients ( 21 , 25 , 26 ). Besides, the neurosensory system is under discussion as further point of action of radon, as it is able to bind to N-methyl-D-asparte-receptors (NMDARs) just like the noble gas xenon, which is commonly used as anaesthetic in the clinic.…”