Anti-inflammatory activity of non-selective PDE inhibitor aminophylline on the lung tissue and respiratory parameters in animal model of ARDS

Abstract

Abstract Acute respiratory distress syndrome (ARDS) is a common complication of critical illness characterized by lung inflammation, epithelial and endothelial dysfunction, alveolar-capillary leakage, and worsening respiratory failure. The present study aimed to investigate the anti-inflammatory effects of non-selective phosphodiesterase (PDE) inhibitor aminophylline. New Zealand white rabbits were randomly divided into 3 groups: animals with respiratory failure defined as PaO2/FiO2 ratio (P/F) below < 26.7 kPa, and induced by saline lung lavage (ARDS), animals with ARDS treated with intravenous aminophylline (1 mg/kg; ARDS/AMINO), and healthy ventilated controls (Control). All animals were oxygen ventilated for an additional 4 h and respiratory parameters were recorded regularly. Post mortem, the lung tissue was evaluated for oedema formation, markers of inflammation (tumor necrosis factor, TNFα, interleukin (IL)-1β, -6, -8, -10, -13, -18), markers of epithelial damage (receptor for advanced glycation end products, RAGE) and endothelial injury (sphingosine 1-phosphate, S1P), oxidative damage (thiobarbituric acid reactive substances, TBARS, 3-nitrotyrosine, 3NT, total antioxidant capacity, TAC). Aminophylline therapy decreased the levels of pro-inflammatory cytokines, markers of epithelial and endothelial injury, oxidative modifications in lung tissue, reduced lung oedema, and improved lung function parameters compared to untreated ARDS animals. In conclusion, non-selective PDE inhibitor aminophylline showed a significant anti-inflammatory activity suggesting a potential of this drug to be a valuable component of ARDS therapy.

Keywords

• Non-selective phosphodiesterase inhibitor
• Aminophylline
• ARDS model
• Lung function
• Inflammation