Key Point:

TNFα-induced release of IL-8 and GROα, two neutrophil chemoattractants, from primary bronchial epithelial cells is significantly greater in smokers with COPD than in smokers without airway obstruction.

REGENSBURG, GERMANY—A new study may help explain why only a small percentage of smokers—15% to 20%—develop chronic obstructive pulmonary disease (COPD). Christian Schulz, MD, and coworkers found that primary bronchial epithelial cells (PBECs) from smokers with COPD produce markedly more interleukin 8 (IL-8) and growth-related oncogene α (GROα) in response to inflammatory stimulation than do PBECs from smokers without airflow limitation.[1]

These investigators also showed that steady-state expression of the tumor necrosis factor α (TNFα)-receptor subtypes TNF-R55 and TNF-R75 did not differ between the two groups. “It therefore appears that the bronchial epithelium of COPD patients reacts to inflammatory stimuli in a way that is COPD-specific and may lead to chronic airway inflammation and airflow limitation,” said Dr. Schulz, a staff physician in the Internal Medicine Clinic at the University of Regensburg in Germany.

The subjects in the study included eight smokers with stage II COPD and eight smokers with normal airflow. All of the subjects had undergone bronchoscopy, usually because of a suspected carcinoma, and thus bronchial epithelial samples containing PBECs were available. The investigators focused their analysis on PBEC release of IL-8 and GROα because the bronchial epithelium is the body’s first line of defense against tobacco smoke and the two chemokines are strong neutrophil chemoattractants.

At baseline, messenger RNA (mRNA) expression of IL-8 and GROα in the PBECs was not significantly different in the two groups. After four hours of TNFα stimulation, however, median mRNA expression of IL-8 rose to 12.9% of the β-actin value in the COPD patients but to only 4.6% of the β-actin value in the other smokers. Similar results were found for GROα expression.

These increases were accompanied by elevations in IL-8 and GROα protein levels. Again, the elevations were markedly higher in the COPD group than in the other group.

By contrast, stimulation of PBECs with interferon-γ had no effect on mRNA expression of IL-8 or GROα or on the release of the two chemokines in either group. Furthermore, no significant differences in TNF-R55 or TNF-R75 expression were observed between the groups when TNFα subtype expression was quantified at the steady-state mRNA level.

The extent of IL-8 and GROα release was found to correlate strongly—albeit inversely—with measurements of airway obstruction, such as FEV1 and FEV1/FVC. According to the investigators, this finding supports the concept that the study’s results have functional relevance to the pathogenesis of COPD. They suggested that increased expression of the two chemokines in COPD patients may lead to faster and greater transit of neutrophils from the airway wall and vasculature into the bronchial lumen.

—Timothy Begany

Reference
1. Schulz C, Krätzel K, Wolf K, et al. Activation of bronchial epithelial cells in smokers without airway obstruction and patients with COPD. Chest. 2004;125:1706-1713.

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