Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. The initial step in the inflammatory process is overexpression of adhesion molecules, which leads to excessive transmigration of neutrophils. One of these adhesion molecules is ICAM-1 which is elevated in COPD patients. In this study we evaluated the influence of N-acetylcysteine (NAC) (0.01 mM-30 mM) on the cytokine-induced (TNF-alphalpha/IL-1ß) expression of the ICAM-1 adhesion molecule and on IL-8 release in endothelial (ECV-304) and bronchial epithelial (H292) cell lines. The methodology used consisted of immunochemistry for the assessment of surface ICAM-1 and ELISA method for that of soluble ICAM-1 and IL-8. NAC inhibited the TNF-alphalpha/IL-1ß-stimulated ICAM-1 expression and IL-8 release from both cell lines in a concentration dependent manner. The most effective concentrations were 30 mM and 20 mM (99 and 90% inhibition respectively, P<0.01). We conclude that NAC is an effective inhibitor of TNF-alphalpha/IL-1ß- stimulated ICAM-1 and IL-8 release in endothelial and epithelial cells. This fact highlights the anti-inflammatory potential of NAC in COPD.
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Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation. Cigarette smoke has been considered a major player in the pathogenesis of COPD. The inflamed airways of COPD patients contain several inflammatory cells. Vitamin A metabolites have been implicated in the repair of lung damage. Exposure to cigarette smoke has been shown to depress levels of retinol in lungs of rats. The purpose of this study was to investigate if a low, but not deficient, vitamin A status potentiated susceptibility to the development of cigarette smoke-induced lung emphysema in mice. Mice were bred that were the offspring’s of 3 generations of mice that were fed a purified diet containing low levels of vitamin A and exposed to cigarette smoke for 3 months, every weekday. Then, levels of 9-cis, 13-cis, and all-trans retinoic acid, retinol and retinyl palmitate were measured in plasma, liver and right lung lobe. The left lung lobe was used to assess mean linear intercept (Lm), as a measure of smoke-induced lung damage. Average feed intakes were not different between treatment groups. We show that both retinol and retinyl palmitate levels were dramatically decreased in the storage organs of mice on the low vitamin A diet (retinol 2-fold in both lung and liver, and retinyl palmitate 5- fold in lung) which shows that the depletion was successful. However, this treatment did not result in the development of lung emphysema. However, smoke exposure led to a significant increase in Lm in mice with a low vitamin A status compared to the room air-breathing controls. Lung levels of acid retinoids were similar in all mice, irrespective of diet or smoke exposure. Concluding, a low vitamin A status increases the susceptibility to the development of cigarette smoke-induced lung emphysema, possibly because of decreased anti-oxidant capacity in the lungs due to locally reduced retinol and retinyl palmitate levels. These observations indicate that human populations with a low vitamin A status and a high prevalence of smoking may be at increased risk of developing lung emphysema.
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