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You are here : 3-RX.com > Home > Infections - Urine Problems -

Reason for cystic fibrosis infections uncovered

Infections • • Urine ProblemsMar 31, 08

People with cystic fibrosis are prone to lung infections, especially with the bug Pseudomonas aeruginosa, and now a German team has discovered why. Their experiments with mice show that the accumulation of a fatty substance called ceramide in the respiratory tract is the reason.

The good news is that one enzyme, dubbed Asm, is in large part responsible for this build-up, so treatment aimed at blocking this enzyme might reduce lung infections in people with CF.

The underlying cause of the disease cystic fibrosis is known to be a gene mutation, but how this promotes lung infections was unclear.

“We show for the first time that an increase of ceramide is critically involved,” Dr. Erich Gulbins told Reuters Health. “We further provide potential mechanisms how ceramide could contribute to the development of Pseudomonas aeruginosa infections in cystic fibrosis patients.

Using mice, Gulbins, from the University of Duisburg-Essen in Germany, and colleagues show that the cystic fibrosis mutation leads to changes that favors the production of ceramide via the action of Asm rather than the clearance of ceramide by another enzyme. The net result is accumulation of ceramide in the respiratory tract, according to the team’s report in the research journal Nature Medicine.

Further testing showed that the ceramide build-up caused lung inflammation, the death of cells lining the airways, and susceptibility to Pseudomonas aeruginosa infections.

It turns out that the antidepressant amitriptyline is an Asm blocker. The researchers found that mice given amitriptyline had normal ceramide levels in the lungs, did not show typical signs of cystic fibrosis, and were not at increased risk for infection.

Gulbins said that his team is now delving further into these findings. They have also “initiated several clinical studies to test whether treatment with amitriptyline is beneficial for patients with cystic fibrosis.”

SOURCE: Nature Medicine, online March 30, 2008.

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