Ceramide linked to cystic fibrosis vulnerability to lung infection

A drug used to treat depression may be able to prevent lung infections in patients with cystic fibrosis, claim German researchers.

In mice studies, they found that the tricyclic antidepressant amitriptyline reduced the risk of potentially fatal bacterial lung infections in cystic fibrosis patients.

The study centred on a lipid called ceramide, which was found in higher levels in the lungs of mice genetically engineered to have cystic fibrosis than healthy mice.  

Bacterial lung infections were also found to be more common in the mice with the highest levels of ceramide.

To test whether these findings were relevant for humans, the researchers isolated nasal respiratory epithelial cells from 18 cystic fibrosis patients and 17 healthy individuals. The cells were stained using monoclonal antibodies for ceramide. 

This showed an accumulation of ceramide in cells taken from cystic fibrosis patients, but not the healthy patients.

Looking for drugs that could reduce the production of ceramide, the researchers identified amitriptyline as having a know ceramide-lowering effect. 

Amitriptyline 10mg/kg was injected twice daily for two and a half days in cystic fibrosis mice and successfully reduced ceramide levels.


Nature Med Online 2008

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