title: Effect of total body irradiation on late lung effects: hidden dangers.
abstract: OBJECTIVE
  In our ongoing investigation into the consequences of a radiological terrorism or nuclear dispersion event, we assessed whether a dose range that is believed to be sub-threshold for the development of lung endpoints results in late pathological changes and, secondarily, whether those late changes affect the lung's ability to respond to subsequent challenge.
  
  
  METHODS
  C57BL/6J mice received total body irradiation (0.5-10 Gy) and were followed for 6-18 months after irradiation. At 12 and 15 months, a subset of mice was exposed to a second challenge (aerosolised lipopolysaccharide [LPS]).
  
  
  RESULTS
  Cytokines shown to be upregulated early (hours) following irradiation (interleukin [IL]6, keratinocyte chemoattractant [KC], IL1B, and IL1R2) demonstrated increases in messenger ribose nucleic acid (mRNA) expression at late time points, beginning at nine months. Although persistent, dose-dependent increases in T cell counts were seen, no other overt changes in pathophysiology were observed. Nonetheless, animals that were exposed to a secondary challenge at late time points demonstrated an increased inflammatory cell recruitment and persistence in response relative to controls.
  
  
  CONCLUSIONS
  We propose that, following doses that elicit little change in pathophysiology, sub-clinical radiation-induced injury increases the lungs' susceptibility to a secondary challenge, possibly through a radiation-induced alteration in the immune defense system.
authors.affiliation: Departments of Pediatrics and Neonatology, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Johnston
authors.forename: Casey
authors.initials: C
authors.lastname: Manning
authors.forename: Eric
authors.initials: E
authors.lastname: Hernady
authors.forename: Christina
authors.initials: C
authors.lastname: Reed
authors.forename: Sally W
authors.initials: SW
authors.lastname: Thurston
authors.forename: Jacob N
authors.initials: JN
authors.lastname: Finkelstein
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D019583:Dose Fractionation, Radiation; D008168:Lung / Q000473:pathology / Q000503:physiopathology* / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017564:Radiation Pneumonitis / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000528:radiation effects*; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D016207:Cytokines