Influence of Long-Term Inhaled Glucocorticoids on the Lung Surfactant Phospholipid Levels in Rats

Abstract

Background: Damage to lung surfactant, which is responsible for the lung local immunity, may contribute to the development of bronchial inflammation in patients with bronchial asthma. Different doses of glucocorticoids produce a stimulating or inhibiting effect on the synthesis of the surfactant protein (SP-A) mRNA. Lung surfactant disorders may negatively influence bronchial homeostasis and aggravate the condition of patients with bronchial asthma and COPD. The objective of this study was to evaluate the influence of long-term inhaled corticosteroids on the phospholipid levels of the lung surfactant in rats. Methods and Results: Inhalations of prednisolone hemisuccinate (PH) were given to white non-pedigree rats weighing 180-200g at a dose of 0.3mg/kg daily for 30 days. Already by the end of the first study period (10 days), lung surfactant phospholipid levels were found to decrease significantly from 1.35±0.060mg to 1.02±0.045mg (P<0.001). The decrease was further recorded at Day 20 and Day 30 of the inhalation period: down to 0.94±0.042 mg (P<0.001) and 1.04±0.047mg (P<0.01), respectively. The phospholipid content continued to decrease after termination of inhalations down to 0.80±0.036mg (P<0.001) and 0.63±0.028mg (P<0.001) at Day 40 and 50 of the experiment. By Day 60 of the experiment (30 days after termination of PH), the phospholipid content in the lung surfactant was restored to the baseline level of 1.29±0.058mg. Conclusion: The content of lung surfactant was found to decrease significantly as a result of long-term ICS treatment, which may have a negative effect for chronic lung diseases.

Keywords

• inhaled corticosteroids;
• lung surfactant;
• COPD;
• bronchial asthma;
• phospholipid content