Evaluation of systemic markers of inflammation in atomic‐bomb survivors with special reference to radiation and age effects

Abstract

Past exposure to atomic bomb (A-bomb) radiation has exerted various long-lasting deleterious effects on the health of survivors. Some of these effects are seen even after >60 yr. In this study, we evaluated the subclinical inflammatory status of 442 A-bomb survivors, in terms of 8 inflammation-related cytokines or markers, comprised of plasma levels of reactive oxygen species (ROS), interleukin (IL)-6, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), IL-4, IL-10, and immunoglobulins, and erythrocyte sedimentation rate (ESR). The effects of past radiation exposure and natural aging on these markers were individually assessed and compared. Next, to assess the biologically significant relationship between inflammation and radiation exposure or aging, which was masked by the interrelationship of those cytokines/markers, we used multivariate statistical analyses and evaluated the systemic markers of inflammation as scores being calculated by linear combinations of selected cytokines and markers. Our results indicate that a linear combination of ROS, IL-6, CRP, and ESR generated a score that was the most indicative of inflammation and revealed clear dependences on radiation dose and aging that were found to be statistically significant. The results suggest that collectively, radiation exposure, in conjunction with natural aging, may enhance the persistent inflammatory status of A-bomb survivors.

Cardiovascular diseases related to ionizing radiation: The risk of low-dose exposure (Review)

“…Apart from the induction of adhesion molecules, the levels of cytokines such as interleukin (IL)-6 and IL-8, and other inflammatory molecules, such as transforming growth factor-β (TGF-β), were shown to increase after high and moderate irradiation (93,94). In addition, the Japanese atomic bomb survivors' cohort showed signs of a general increased state of inflammation, with increased levels of IL-6 and C-reactive protein (CRP) (95). In addition to pro-inflammatory responses, there is evidence of pro-thrombotic changes after irradiation of the endothelium.…”

Low-dose ionising radiation and cardiovascular diseases – Strategies for molecular epidemiological studies in Europe

“…One of its three main scientific questions deals with non- 49 cancer effects, such as CVD or cataracts at doses below 0.5 Gy. 50 Currently, the evidence from epidemiological studies for a causal 51 relationship between ionising radiation and CVD risk at doses 52 below 0.5 Gy is weak and the underlying biological mechanisms 53 not understood [20] -indeed they are not delineated even at 54 higher doses, although plausible inflammatory explanations have 55 been hypothesised [2]. An increased risk at low ionising radiation 56 doses would have major implications for radiation protection of 57 the public, radiation-exposed workers and patients.…”

“…Cohort failure mortality [51], and in long-term levels of inflammatory 149 markers [52][53][54] have also been found among atomic-bomb 150…”

Preventive or Potential Therapeutic Value of Nutraceuticals against Ionizing Radiation-Induced Oxidative Stress in Exposed Subjects and Frequent Fliers

“…Some suggested that the health risks of doses of less than 10 cGy cannot be measured, while others claimed that no dose of ionizing radiation can be considered completely safe and that the use of radiation must always be determined on the basis of risk versus benefit [12–15]. However, the former idea ignores the effect of interaction between radiation-induced stress and other stress conditions that may enhance diseases and the risk of oxidative stress-induced cancer, particularly in ageing patients [5,6,16–18]. …”

“…The evidence suggests a strong association between cardiovascular disease, ageing and exposure to low-to-moderate levels of radiation [5,6]. Other clinically important consequences of exposure to radiation are retina degeneration and eye cataracts, which were previously thought to be deterministic or tissue reactions but are currently recognized as possibly stochastic in nature and determined by much lower radiation levels than previously believed [33–35].…”