Gene Protects Newborns from Killer Respiratory Disease (1/5/2008)

Yale School of Medicine researchers have isolated a gene that helps protect newborns from the most common respiratory cause of infant death in the United States-respiratory distress syndrome.

This gene, macrophage migration inhibitory factor (MIF), also helps fetal lungs develop, the researchers report this month in the Journal of Immunology.

The overt cause of respiratory distress syndrome is underdeveloped lungs-the more premature the newborns, the more likely they are to have a loss of lung volume caused by air space collapse and poorly developed capillaries. Infants with the syndrome often require mechanical ventilation within the first hours of life.

The Yale team wanted to pinpoint the molecular events leading to respiratory distress syndrome because, despite advances in treatment, survivors often develop chronic lung disease and are at higher risk of developing asthma.

"The finding is important because prematurity is not only the most common respiratory cause of infant mortality in the U.S., it also tends to be a more serious problem in inner city neighborhoods," said Richard Bucala, M.D., professor of medicine and pathology, professor of epidemiology at Yale School of Public Health, and senior author of the study.

The research team studied premature mouse pups bred to be deficient in MIF and found that the lungs of these mice were less developed. The mice also had lower levels of vascular endothelial growth factor and corticosterone-two factors that promote lung development.

In addition to its role in fetal lung development, the MIF gene also regulates the innate immune response and has been implicated in a number of inflammatory disorders, such as sepsis, acute respiratory distress syndrome in adults, asthma, and autoimmune diseases.

"Because relationships exist between the known human variants of MIF and the severity of other respiratory diseases such as asthma and cystic fibrosis, we are very interested to know whether MIF variants might be associated with a higher risk for developing respiratory distress syndrome or chronic lung disease in premature infants," said Alia Bazzy-Asaad, chief of the pediatric pulmonary section at Yale School of Medicine and co-author of the study. "We hope to pursue this in future studies."

Co-authors include Katherine Kevill, Vineet Bhandari, Mika Kettunen, Lin Leng, Juan Fan, Yuka Mizue, James Dzuira, Miguel Reyes-Mugica, Courtney McDonald, John Baugh, Christine O'Connor, Zubair Aghai, and Seamas Donnelly.

Note: This story has been adapted from a news release issued by Yale University

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