title: Examining the Effects of External or Internal Radiation Exposure of Juvenile Mice on Late Morbidity after Infection with Influenza A.
abstract: A number of investigators have suggested that exposure to low-dose radiation may pose a potentially serious health risk. However, the majority of these studies have focused on the short-term rather than long-term effects of exposure to fixed source radiation, and few have examined the effects of internal contamination. Additionally, very few studies have focused on exposure in juveniles, when organs are still developing and could be more sensitive to the toxic effects of radiation. To specifically address whether early-life radiation injury may affect long-term immune competence, we studied 14-day-old juvenile pups that were either 5 Gy total-body irradiated or injected internally with 50 μCi soluble (137)Cs, then infected with influenza A virus at 26 weeks after exposure. After influenza infection, all groups demonstrated immediate weight loss. We found that externally irradiated, infected animals failed to recover weight relative to age-matched infected controls, but internally (137)Cs contaminated and infected animals had a weight recovery with a similar rate and degree as controls. Externally and internally irradiated mice demonstrated reduced levels of club cell secretory protein (CCSP) message in their lungs after influenza infection. The externally irradiated group did not recover CCSP expression even at the two-week time point after infection. Although the antibody response and viral titers did not appear to be affected by either radiation modality, there was a slight increase in monocyte chemoattractant protein (MCP)-1 expression in the lungs of externally irradiated animals 14 days after influenza infection, with increased cellular infiltration present. Notably, an increase in the number of regulatory T cells was seen in the mediastinal lymph nodes of irradiated mice relative to uninfected mice. These data confirm the hypothesis that early-life irradiation may have long-term consequences on the immune system, leading to an altered antiviral response.
authors.affiliation: a  Department of Pediatrics and Neonatology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Misra
authors.affiliation: a  Department of Pediatrics and Neonatology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.|b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Johnston
authors.affiliation: b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Groves
authors.affiliation: c  Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Marta L
authors.initials: ML
authors.lastname: DeDiego
authors.affiliation: d  Department of Environmental Health and Safety: Radiation Safety Unit, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Joe
authors.initials: J
authors.lastname: St Martin
authors.affiliation: b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Christina
authors.initials: C
authors.lastname: Reed
authors.affiliation: b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Eric
authors.initials: E
authors.lastname: Hernady
authors.affiliation: b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Jen-Nie
authors.initials: JN
authors.lastname: Miller
authors.affiliation: e  Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Tanzy
authors.initials: T
authors.lastname: Love
authors.affiliation: a  Department of Pediatrics and Neonatology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.|b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
authors.affiliation: b  Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
mesh_terms: D000375:Aging; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D002588:Cesium Radioisotopes; D018932:Chemokine CCL2 / Q000032:analysis; D007107:Immune System / Q000528:radiation effects*; D009980:Influenza A virus; D051379:Mice; D008810:Mice, Inbred C57BL; D009017:Morbidity; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000528:radiation effects; D014598:Uteroglobin / Q000032:analysis; D014916:Whole-Body Irradiation
chemical_list: D000914:Antibodies, Viral; D002588:Cesium Radioisotopes; D018932:Chemokine CCL2; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin