Dependence on O2- generation by xanthine oxidase of pathogenesis of influenza virus infection in mice

J Clin Invest. 1990 Mar;85(3):739-45. doi: 10.1172/JCI114499.


We evaluated various biochemical parameters in influenza virus-infected mice and focused on adenosine catabolism in the supernatant of bronchoalveolar lavage fluid (s-BALF), lung tissue, and serum (plasma). The activities of adenosine deaminase (ADA) and xanthine oxidase (XO), which generates O2-, were elevated in the s-BALF, lung tissue homogenate, and serum (plasma). The elevations were most remarkable in s-BALF and in lung tissue: We found a 170-fold increase in ADA activity and a 400-fold increase in XO activity as measured per volume of alveolar lavage fluid. The ratio of activity of XO to activity of xanthine dehydrogenase in s-BALF increased from 0.15 +/- 0.05 (control; no infection) to 1.06 +/- 0.13 on day 6 after viral infection. Increased levels of various adenosine catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) in serum and s-BALF were confirmed. We also identified O2- generation from XO in s-BALF obtained on days 6 and 8 after infection, and the generation of O2- was enhanced remarkably in the presence of adenosine. Lastly, treatment with allopurinol (an inhibitor of XO) and with chemically modified superoxide dismutase (a scavenger of O2-) improved the survival rate of influenza virus-infected mice. These results indicate that generation of oxygen-free radicals by XO, coupled with catabolic supply of hypoxanthine from adenosine catabolism, is a pathogenic principle in influenza virus infection in mice and that a therapeutic approach by elimination of oxygen radicals thus seems possible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / metabolism
  • Adenosine Deaminase / analysis
  • Allopurinol / pharmacology
  • Animals
  • Bronchoalveolar Lavage Fluid / metabolism
  • Male
  • Mice
  • Orthomyxoviridae Infections / etiology*
  • Orthomyxoviridae Infections / metabolism
  • Superoxide Dismutase / pharmacology
  • Superoxides / metabolism*
  • Virus Replication
  • Xanthine Oxidase / analysis
  • Xanthine Oxidase / physiology*


  • Superoxides
  • Allopurinol
  • Superoxide Dismutase
  • Xanthine Oxidase
  • Adenosine Deaminase
  • Adenosine