Radon inhalation reduces LPS-induced pneumonia symptoms in mice and promotes immunosuppression in the lung.

Abstract

Radon, a naturally occurring radioactive noble gas, remains an established component of European balneological medicine in the management of inflammatory diseases. Similarly, X-ray-based radiotherapy, known as low-dose radiation therapy (LDRT), is used. However, the use of both radon therapy and LDRT, remains controversial, even though it was used in some countries to treat patients during the COVID-19 pandemic. This raises the question of the effectiveness of LDRT, especially against inflammatory lung diseases. Previously, we could show in mice that X-ray LDRT has anti-inflammatory and immunosuppressive effects in the management of pneumonia. Our study presented here aimed to assess the effect of radon inhalation on murine pneumonia induced by intratracheal administration of lipopolysaccharide (LPS). Mice were treated with either radon or dexamethasone, the latter being the standard of care for inflammatory diseases. Both treatments improved clinical signs, general health condition and lung architecture in mice with LPS-induced pneumonia. Mechanistically, both treatments downregulated inflammatory pathways and promoted those related to tissue repair and integrity. In both treatment groups, the Th1-proinflammatory response was suppressed and a Th2-anti-inflammatory one was promoted. Interestingly, radon inhalation promoted the anti-inflammatory 'alternative' activation profile of lung macrophages. Furthermore, the assessment of the potential of radon to induce oncogene expression and thereby to increase the risk of cancer development following exposure, showed significant downregulation of oncogenes. In sum, our data provides indications for the effective use of radon in treatment of pneumonia as an alternative for patients who are refractory to dexamethasone treatment or unable to receive corticosteroids due to contraindications.