Excess Oxygen Worsens Lung Inflammation

A new study has shown that oxygen therapy intended to help mice with acute lung inflammation to breathe had the opposite affect, worsening their illness.

The excess oxygen appeared to thwart a natural process that limits lung tissue damage. Previous research showed that inflammation leads to a drop in oxygen levels in the inflamed tissues, which 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 inflammatory molecules. These findings suggested that oxygen given to patients with acute lung inflammation might short-circuit this protective pathway by preventing oxygen levels from dropping enough to trigger the inflammation stop signal.

Senior author Michail Sitkovsky, Ph.D., and colleagues at the U.S. National Institute of Allergy and Infectious Diseases (NIAID, Bethesda, MD, USA) explored this possibility by inducing lung inflammation in three groups of mice. The first group received no supplemental oxygen. Although these mice sustained moderate lung damage, only two died. Another group of 15 mice with acute lung inflammation were treated with either 100% or 60% oxygen for 48 hours. These mice suffered very extensive lung damage, and 11 of the 15 died. A third group of 15 mice with acute lung inflammation were treated with 100% oxygen and an adenosine-like drug to compensate for the oxygen-induced loss of natural adenosine. Only two mice in this group died.

Highly pure oxygen therapy without the addition of an adenosine substitute worsens pre-existing lung inflammation, concluded the researchers. "We suggest that these adenosine substitutes be evaluated for their possible usefulness in settings of acute lung inflammation due to infection or other causes, such as asthma or surgical trauma,” said Dr. Sitkovsky, who is continuing his research at Northeastern University (Boston, MA, USA). His paper was published in the May 2, 2005, issue of PLoS Biology.