Study reveals important new factor in cystic fibrosis lung inflammation

CINCINNATI -- Scientists at Cincinnati Children's Hospital Medical Center have identified a missing piece of the puzzle of how lung damage occurs in cystic fibrosis (CF).

CF is a life-threatening, genetic disease that causes chronic lung infections and impairs digestion. The discovery, published in the current issue of Nature Immunology, provides impetus for the development of novel therapeutics that decrease inflammation in children with CF.

The Cincinnati Children's team found a deficiency in the airways of children with CF of a class of molecules called lipoxins, which are key regulators of inflammation. "When we give analogs of this molecule (lipoxin-like molecules) in mouse models of CF, the molecules do what we'd like them to do -- suppress acute inflammation, switch on the chronic inflammatory process and ameliorate disease -- suggesting that this class of molecules might have therapeutic potential in CF," says Christopher Karp, MD, director of Molecular Immunology at Cincinnati Children's and the study's main author.

Over time, the persistent combination of infection and inflammation in CF lungs leads to their destruction. Several studies in recent years suggest that the frequent and prolonged airway inflammation in CF lungs leads to the eventual cardio-respiratory failure that is the primary cause of death in people with CF.

"It's traditionally been thought that the basic problem in the CF lung is an inability to clear bacteria, with infection leading secondarily to lung-damaging inflammation," says Dr. Karp. "Recent studies suggest it may well be the other way around: abnormally vigorous and prolonged airway inflammatory may be a primary problem. Such responses are inefficient at clearing bacteria, may damage the airway in ways that promote colonization with bacteria, and over time lead to airway destruction.

"It's clear that the inflammatory response of the airway in CF patients is abnormal from th

Contact: Jim Feuer
Cincinnati Children's Hospital Medical Center

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