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Excess oxygen worsens lung inflammation in mice

Research performed at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, has revealed that oxygen therapy aimed at helping mice with acute lung inflammation breathe paradoxically worsened their illness. The researchers say excess oxygen appears to thwart a natural process that limits lung tissue damage. They overcame this deleterious side effect, however, by adding an inhaled anti-inflammatory drug to the oxygen therapy.

"This research illustrates, in an animal model, a delicate balance between supplemental oxygen therapy and an innate tissue-preserving process that appears to operate best in low-oxygen conditions," says NIAID Director Anthony S. Fauci, M.D.

Michail Sitkovsky, Ph.D., senior author of the paper published this week in the journal PLoS Biology, believes the findings could have clinical implications. Supplemental oxygen is a life-saving therapy for patients with breathing problems, but it can harm the lungs if it is used for long periods. While the problem of oxygen-induced lung damage is well known, the biochemical processes leading to this damage have not been fully explained. Dr. Sitkovsky's research reveals a possible mechanism behind this oxygen-induced damage and also provides evidence of a simple way to prevent it.

The current study extends research published in 2001 by Dr. Sitkovsky and colleagues into the role played by the molecule adenosine in regulating inflammation. Inflammatory chemicals produced by the immune system in response to infection or injury must eventually be switched off so that excessive tissue damage can be avoided. Dr. Sitkovsky and his colleagues have shown that inflammation leads to a drop in oxygen levels in the inflamed tissues. This, in turn, triggers the release of adenosine from surrounding cells. When adenosine binds to cell receptors in the inflamed region, it serves as a tissue-protecting stop signal, slowing the flood of damaging
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
2-May-2005


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