Lung irradiation increases mortality after influenza A virus challenge occurring late after exposure

Int J Radiat Oncol Biol Phys. 2013 May 1;86(1):128-35. doi: 10.1016/j.ijrobp.2012.10.019. Epub 2012 Nov 27.

Abstract

Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury.

Methods and materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed.

Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema.

Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / immunology
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Chemokines / immunology
  • Cytokines / immunology
  • Disease Models, Animal
  • Dose-Response Relationship, Radiation
  • Female
  • Hematopoietic Stem Cells / radiation effects
  • Immunity, Innate / immunology
  • Immunoglobulin G / analysis
  • Immunoglobulin G / immunology
  • Influenza A virus* / immunology
  • Lung / immunology
  • Lung / radiation effects*
  • Lung / virology
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / mortality*
  • Orthomyxoviridae Infections / virology
  • Proteins / analysis
  • Weight Loss
  • Whole-Body Irradiation / adverse effects

Substances

  • Chemokines
  • Cytokines
  • Immunoglobulin G
  • Proteins