Radiation dose-dependent increases in inflammatory response markers in A-bomb survivors.
OBJECTIVE
The well-documented increases in malignant tumours in the A-bomb survivors have recently been supplemented by reports that non-cancer diseases, including cardiovascular disease, may also have increased in incidence with increasing radiation dose. Given that low-level inflammatory responses are widely accepted as a significant risk factor for such diseases, we undertook a detailed investigation of the long-term effects of ionizing radiation on the levels of the inflammatory markers C-reactive protein (CRP) and interleukin 6 (IL-6) in A-bomb survivors.


METHODS
Blood samples were taken from 453 participants in a long-term epidemiological cohort of A-bomb survivors. Plasma levels of CRP and IL-6 were measured using standard antibody-mediated procedures. Relationships between CRP or IL-6 levels and radiation dose were then investigated by multivariate regression analysis. Blood lymphocytes from each individual were used for immunophenotyping by flow cytometry with murine monoclonal antibodies to CD3, CD4 and CD8.


RESULTS
CRP levels were significantly increased by about 31% Gy(-1) of estimated A-bomb radiation (p=0.0001). Higher CRP levels also correlated with age, male gender, body mass index and a history of myocardial infarction. After adjustments for these factors, CRP levels still appeared to have increased significantly with increasing radiation dose (about 28% increase at 1Gy, p=0.0002). IL-6 levels also appeared to have increased with radiation dose by 9.3% at 1Gy (p=0.0003) and after multiple adjustments by 9.8% at 1Gy (p=0.0007). The elevated CRP and IL-6 levels were associated with decreases in the percentages of CD4(+) helper T-cells in peripheral blood lymphocyte populations.


CONCLUSIONS
Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.
Hayashi
T
T
Department of Radiobiology, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami Ward, Hiroshima 732-0815 Japan. tomo@rerf.or.jp
Kusunoki
Y
Y
Hakoda
M
M
Morishita
Y
Y
Kubo
Y
Y
Maki
M
M
Kasagi
F
F
Kodama
K
K
Macphee
D G
DG
Kyoizumi
S
S
D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D015331:Cohort Studies; D004307:Dose-Response Relationship, Radiation; D005260:Female; D049673:History, 20th Century; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007564:Japan; D008297:Male; D008875:Middle Aged; D009689:Nuclear Warfare / Q000266:history; D012307:Risk Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000528:radiation effects
D018836:Inflammation Mediators; D015850:Interleukin-6; D002097:C-Reactive Protein