title: Acute adaptive immune response correlates with late radiation-induced pulmonary fibrosis in mice.
abstract: BACKGROUND
  The lung response to radiation exposure can involve an immediate or early reaction to the radiation challenge, including cell death and an initial immune reaction, and can be followed by a tissue injury response, of pneumonitis or fibrosis, to this acute reaction. Herein, we aimed to determine whether markers of the initial immune response, measured within days of radiation exposure, are correlated with the lung tissue injury responses occurring weeks later.
  
  
  METHODS
  Inbred strains of mice known to be susceptible (KK/HIJ, C57BL/6J, 129S1/SvImJ) or resistant (C3H/HeJ, A/J, AKR/J) to radiation-induced pulmonary fibrosis and to vary in time to onset of respiratory distress post thoracic irradiation (from 10-23 weeks) were studied. Mice were untreated (controls) or received 18 Gy whole thorax irradiation and were euthanized at 6 h, 1d or 7 d after radiation treatment. Pulmonary CD4+ lymphocytes, bronchoalveolar cell profile & cytokine level, and serum cytokine levels were assayed.
  
  
  RESULTS
  Thoracic irradiation and inbred strain background significantly affected the numbers of CD4+ cells in the lungs and the bronchoalveolar lavage cell differential of exposed mice. At the 7 day timepoint greater numbers of pulmonary Th1 and Th17 lymphocytes and reduced lavage interleukin17 and interferonγ levels were significant predictors of late stage fibrosis. Lavage levels of interleukin-10, measured at the 7 day timepoint, were inversely correlated with fibrosis score (R=-0.80, p=0.05), while serum levels of interleukin-17 in control mice significantly correlated with post irradiation survival time (R=0.81, p=0.04). Lavage macrophage, lymphocyte or neutrophil counts were not significantly correlated with either of fibrosis score or time to respiratory distress in the six mouse strains.
  
  
  CONCLUSIONS
  Specific cytokine and lymphocyte levels, but not strain dependent lavage cell profiles, were predictive of later radiation-induced lung injury in this panel of inbred strains.
authors.affiliation: Department of Human Genetics, Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada. alexandra.paun@gmail.com.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Paun
authors.affiliation: Department of Human Genetics, Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada. kunamit@gmail.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Kunwar
authors.affiliation: Department of Human Genetics, Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada. christina.haston@mcgill.ca.|Department of Medicine, Meakins-Christie Laboratories, McGill University, 3626 St. Urbain, H2X 2P2, Montreal, QC, Canada. christina.haston@mcgill.ca.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Haston
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005720:Gamma Rays / Q000009:adverse effects*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000209:etiology*; D011832:Radiation Injuries / Q000209:etiology*; D017564:Radiation Pneumonitis / Q000209:etiology*; D013909:Thorax / Q000276:immunology* / Q000528:radiation effects
chemical_list: D016207:Cytokines