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Title: Dornase Alpha (Pulmozyme) May Reduce Inflammation for Cystic Fibrosis: Presented at ACAAI

"Dornase Alpha (Pulmozyme) May Reduce Inflammation for Cystic Fibrosis: Presented at ACAAI"

By Crystal Phend ANAHEIM, CA -- November 24, 2005 -- Dornase alpha (Pulmozyme) may pull double-duty as an anti-inflammatory agent for the chronic lung infections of cystic fibrosis, researchers said here at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI). Dornase alpha (rhDNase) is commonly used in cystic fibrosis patients to clear the thick, sticky mucus that accumulates in the airways and leads to infection with colonizing bacteria like Pseudomonas aeruginosa. Once an infection occurs, antibiotics are used to control the bacteria and avoid chronic infection. "Chronic Pseudomonas infection in cystic fibrosis patients can lead to inflammation and amplified cytokine expression," said lead author Archana R. Narayan, MD, Fellow, Nassau University Medical Center, East Meadow, New York, United States, who presented study findings on dornase alpha on November 6[^th.

Dr. Narayan and colleagues conducted a small study to look at markers of lung inflammation in cystic fibrosis patients and healthy subjects serving as controls.

Some of the patients in the cystic fibrosis group had already been taking dornase alpha prior to study entry, but their baseline characteristics were similar to patients who had not previously taken the drug.

The researchers gathered peripheral blood mononuclear cells from both groups. The cells were then cultured with bronchial epithelial cells stimulated with P. aeruginosa lipopolysaccharide, a special molecule in the bacteria's outer cell membrane. After 24 hours, 10 mcg/mL of dornase alpha was added to the mix.

The researchers measured for levels of pro-inflammatory cytokines, including regulated on activation, normal T expressed and secreted cytokines (RANTES) antibodies and tumor necrosis factor-alpha (TNF-alpha).

Results show that RANTES expression showed a significant mean decrease (from 1.0- to 0.8-fold) in cystic fibrosis patients' cultures treated with dornase alpha compared to Pseudonomas alone (P = .008). In healthy subjects the cultures had increases in RANTES from 1.0- to 1.3-fold.

Cystic fibrosis patients had decreases in TNF-alpha gene expression but the difference was not statistically different from healthy subjects, who showed an increase in the inflammatory TNF-alpha expression.

One issue brought up in a discussion with the audience after presentation was that TNF-alpha is an important part of the immune system and mobilizes white blood cells to fight infections. However, it is also implicated in some chronic conditions in which its constant presence causes tissue damage and pain, such as in rheumatoid arthritis and Crohn's disease.

Dr. Narayan said the role of TNF-alpha in cystic fibrosis is somewhat controversial.

The researcher concluded that dornase alpha may have anti-inflammatory properties in bronchial epithelial cells but that further research is needed.

The study was supported by a research grant from Genentech, Inc.

[Presentation title: RhDNase Decreases P. aeruginosa Lipopolysaccharide (PsLPS) Stimulated RANTES and TNF-alpha Expression from Peripheral Blood Mononuclear Cells (PBMCs) from Cystic Fibrosis (CF) Patients in the Presence of Bronchial Epithelial Cells (BECs). Abstract 18]

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