A single pathway for lung damage

SARS, avian flu, and other lung diseases destroy the lungs via a common mechanism, researcher report in __Cell__ today. That mechanism, based on innate immunity, could provide new targets for treating severe lung damage, the linkurl:researchers say.;http://www.cell.com/content/article/abstract?uid=PIIS0092867408003401 Joseph Penninger, from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences, and colleagues set up an intensive care unit for mice in his lab in order t

Written byEdyta Zielinska
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SARS, avian flu, and other lung diseases destroy the lungs via a common mechanism, researcher report in __Cell__ today. That mechanism, based on innate immunity, could provide new targets for treating severe lung damage, the linkurl:researchers say.;http://www.cell.com/content/article/abstract?uid=PIIS0092867408003401 Joseph Penninger, from the Institute of Molecular Biotechnology of the Austrian Academy of Sciences, and colleagues set up an intensive care unit for mice in his lab in order to study lung failure. They intubated knockout mice and monitored oxygen pressure and tidal volume. Only one mouse, lacking a functioning toll-like receptor 4 (TLR-4), showed a decrease in lung damage. TLR-4 is an important receptor in innate immunity, which signals activation via two pathways, TRIF and MyD88. The researchers found that lung injury was mediated exclusively through the TRIF pathway and not via MyD88. Also, the trigger for TLR-4 turned out to be the oxidation of the animals' own lung surfactant, made up of phospholipids. The oxidized phospholipids activates TLR-4, resulting in the cytokine storm that causes much of the lung damage. In order to see whether their results held true outside of the mouse-ICU, researchers tested human and simian lung samples infected with SARS, H5N1, anthrax and monkey pox and found the oxidized phospholipids in each case. There's no treatment for severe lung injury caused by disease, trauma, or sepsisr said Penninger. "You put people in intensive care, and hope for the best." The current study identifies "steps where you can interfere" with the inflammation pathway to prevent severe lung damage, Penninger said. He has started a company called Apeiron Biologics, which aims to develop treatment for lung failure caused by different conditions. If oxidation of a ubiquitous lung surfactant is dangerous, could patients be harmed if given oxygen in an ICU? Kenneth Chien, Director of the Massachusetts General Hospital cardiovascular research center, noted that oxygen can't be cut out of intensive care treatment, since "it's required for viability." Penninger's research simply "suggests that you would want to titrate the oxygen carefully," he said, and watch for any reaction.
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