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BookmarkScienceDaily (May 4, 2004) — DURHAM, N.C. -- An enzyme that protects the body from reactive chemicals called free radicals is crucial in preventing the inflammation that causes chronic lung disease in premature infants, according to three new studies.
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The findings could lead to improved treatments to alleviate such inflammation, preserving the lungs of premature infants, said Richard Auten, M.D., a neonatalogist and associate professor of pediatrics at Duke University Medical Center. Auten and colleagues from the Medical College of Wisconsin reported their findings in three presentations on May 2 and 3, 2004, at the Pediatric Academic Societies' annual meeting in San Francisco. The research was sponsored by the American Lung Association and the National Institutes of Health.
In studies with mice, the researchers previously found that infant animals with an extra copy of the gene for the crucial enzyme, called superoxide dismutase, were better able to defend themselves against oxygen-free radicals. Oxygen-free radicals are highly reactive forms of oxygen that can readily combine with and damage proteins and other molecules in body tissues such as the lungs. Superoxide dismutase reacts with oxygen-free radicals, converting them into harmless byproducts.
The free radicals that attack lung cells are produced by white blood cells enlisted by the infant's immune system, and are not only a result of the oxygenated air breathed in by babies, according to experiments in lung cells conducted by Auten and his colleagues. This damage to lung cells can be partly prevented by turning on the gene which produces superoxide dismutase, the researchers found.
The fragile lungs of premature babies cannot take in enough air to support life, but supplemental oxygen or ventilation can damage delicate, underdeveloped lung tissue, causing inflammation and respiratory distress. Even exposure to normal room air may overwhelm the lungs of a premature infant, Auten said. The damage triggers the infant's immune system, which sends in a horde of white blood cells that scavenger damaged tissue. But in premature infants, the white blood cells often stay in the lungs too long causing even more damage. The persistent inflammation also delays lung development and robs nutrients from other organs.
"We want to understand how to modify this immune response in a safe way that prevents inflammation but avoids infections and allow normal lung development," Auten said. The key to stopping such inflammation in infant lungs might be superoxide dismutase, he said.
The enzyme may also encourage lung development, Auten and his colleagues found. The transgenic mice with an extra copy of the superoxide dismutase gene had better blood vessel growth in their lungs than normal mice when exposed to a 95 percent oxygen environment for one week.
Inflammation caused by an overactive immune system is not the only source of lung problems for premature infants. Their lungs lack surfactant, a protein that lubricates the lung's surface cells and help keep small air sacs, called alveoli, open and functioning. Most premature babies also have too few alveoli, which prevents their lungs from fully expanding and taking in enough air. Combined with the need for supplemental oxygen or ventilation, these factors lead to respiratory distress syndrome and chronic lung disease.
Currently, there is no good treatment to stop the cascade of injury in which inflammation meant to heal becomes a biochemical attack on the body's own tissue. Steroids can alleviate the inflammation, but the drugs can slow brain and lung growth and impair immune function. The average hospital stay for infants who develop chronic lung disease -- stiff, scarred lungs -- is six months, according to the National Institutes of Health.
Auten's co-authors include Mohamed Ahmed, M.D., fellow, Duke University School of Medicine; Ganesh Konduri, M.D., associate professor of pediatrics, Medical College of Wisconsin; Ann Lee, M.D., fellow, Medical College of Wisconsin; Neil Hogg, Ph.D., associate professor of biophysics, Medical College of Wisconsin; and Rose Verber, research technologist, Medical College of Wisconsin.
