Effects of KF19514, a Phosphodiesterase 4 and 1 Inhibitor, on Bronchial Inflammation and Remodeling in a Murine Model of Chronic Asthma

Abstract

Background: Phosphodiesterase 4 selective inhibitor may prevent airway inflammation and remodeling. Objective: The aim of this study was to investigate the effects of KF19514, a phosphodiesterase 4 and 1 dual inhibitor, on chronic airway inflammation and remodeling following chronic exposure to aerosolized antigen in mice. Methods: Ovalbumin (OVA) was administered intraperitoneally to BALB/c mice on days 0 and 14, and the mice were then exposed to aerosolized OVA daily for 4 weeks. Twenty-four hours following the final inhalation, bronchial responsiveness to acetylcholine was measured, and histologic examination and hydroxyproline content of the lung were evaluated. Results: Bronchial responsiveness to acetylcholine, number of inflammatory cells and eosinophils in the lamina propria, thickness of epithelial and subepithelial collagen layers, and hydroxyproline content of the lung increased following chronic exposure to OVA for 7 weeks. KF19514 significantly prevented all of these changes. Conclusions: Phosphodiesterase 4 and 1 inhibitors such as KF19514 may help prevent bronchial hyperresponsiveness and chronic asthma-induced airway remodeling.

Keywords

• airway hyperresponsiveness
• airway remodeling
• asthma
• murine model
• PDE inhibitor