Increased mortality associated with TCDD exposure in mice infected with influenza A virus is not due to severity of lung injury or alterations in Clara cell protein content

Chem Biol Interact. 2005 Aug 15;155(3):181-90. doi: 10.1016/j.cbi.2005.06.004.


Most studies examining the cause of increased mortality in mice infected with a normally non-lethal dose of influenza A virus after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have focused on defects in the immune system. This study examined other possible consequences of TCDD exposure, which could alter pulmonary inflammation during infection. We measured bronchoalveolar lavage (BAL) fluid lactate dehydrogenase (LDH) and protein concentrations and lung wet to dry weight ratios to assess lung damage and edema formation. Immunohistochemistry for Cyp1A1 was used to evaluate the responsiveness of the lung to TCDD. Additionally, we characterized the effects of TCDD on Clara cell secretory protein (CCSP), which plays a regulatory role in pulmonary inflammation. There were no differences in BAL fluid LDH and protein levels, lung wet to dry weight ratios, or the amount of CCSP in the lungs from mice treated with TCDD or vehicle control. The amount of Cyp1A1 in endothelial cells, Clara cells, and Type II pneumocytes was greatly induced after TCDD exposure. Although lung tissue was clearly responsive to TCDD as shown by Cyp1A1 induction, the increased mortality in infected mice exposed to TCDD did not correlate with increased damage to the lung or decreased CCSP concentrations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A1 / metabolism
  • Female
  • Influenza A virus / pathogenicity*
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / pathology
  • Lung Injury
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / etiology*
  • Orthomyxoviridae Infections / metabolism
  • Orthomyxoviridae Infections / pathology
  • Polychlorinated Dibenzodioxins / toxicity*
  • Uteroglobin / metabolism


  • Polychlorinated Dibenzodioxins
  • Scgb1a1 protein, mouse
  • Uteroglobin
  • Cytochrome P-450 CYP1A1