Immunomodulatory Properties and Molecular Effects in Inflammatory Diseases of Low-Dose X-Irradiation

Abstract

Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.

Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases

“…An aggravated adhesion of innate and adaptive immune cells to the ECs has been reported following LD-RT, accompanied by an increased secretion of the cytokine TGF-β1. In addition, a hampered leukocyte adhesion was most pronounced after a 0.5 Gy exposure and correlated with the expression of X-chromosome linked inhibitor of apoptosis protein (XIAP) and the DNA-binding and transcriptional activity of NF-κB [94,111]. More recently, a non-linear induction of ROS and superoxide dismutase (SOD) activity in EC following irradiation with doses <1.0 Gy has been reported.…”

“…At present, it is widely accepted that LD-RT may change an inflammatory condition to an anti-inflammatory one [92,94,95]. The underlying mechanism(s), however, are still fragmentarily investigated.…”

“…Nevertheless, it is becoming more and more clear that complex mechanisms are involved which are operating interconnectively and in a common dose-dependent manner [96,97]. A non-linear dose relationship exists and has been observed in a multitude of experimental and preclinical model systems [94,98].…”

“…Since the latter has to open the barrier to allow a passage of the immune cells from the blood to the tissue, ECs have a pivotal impact on the immune modulatory effects of LD-RT [94]. An aggravated adhesion of innate and adaptive immune cells to the ECs has been reported following LD-RT, accompanied by an increased secretion of the cytokine TGF-β1.…”

“…It is notable to mention that low-dose irradiation mostly influences cells of the innate immune system as well as endothelial cells (EC) [94]. These cells comprise the key regulators of initiation and resolution of inflammation [99][100][101].…”